Zhao J

References (124)

Title : Soil microbiome of shiro reveals the symbiotic relationship between Tricholoma bakamatsutake and Quercus mongolica - Guo_2024_Front.Microbiol_15_1361117
Author(s) : Guo H , Liu W , Xie Y , Wang Z , Huang C , Yi J , Yang Z , Zhao J , Yu X , Sibirina LA
Ref : Front Microbiol , 15 :1361117 , 2024
Abstract : Tricholoma bakamatsutake is a delicious and nutritious ectomycorrhizal fungus. However, its cultivation is hindered owing to limited studies on its symbiotic relationships. The symbiotic relationship between T. bakamatsutake and its host is closely related to the shiro, a complex network composed of mycelium, mycorrhizal roots, and surrounding soil. To explore the symbiotic relationship between T. bakamatsutake and its host, soil samples were collected from T. bakamatsutake shiro (Tb) and corresponding Q. mongolica rhizosphere (CK) in four cities in Liaoning Province, China. The physicochemical properties of all the soil samples were then analyzed, along with the composition and function of the fungal and bacterial communities. The results revealed a significant increase in total potassium, available nitrogen, and sand in Tb soil compared to those in CK soil, while there was a significant decrease in pH, total nitrogen, total phosphorus, available phosphorus, and silt. The fungal community diversity in shiro was diminished, and T. bakamatsutake altered the community structure of its shiro by suppressing other fungi, such as Russula (ectomycorrhizal fungus) and Penicillium (phytopathogenic fungus). The bacterial community diversity in shiro increased, with the aggregation of mycorrhizal-helper bacteria, such as Paenibacillus and Bacillus, and plant growth-promoting bacteria, such as Solirubrobacter and Streptomyces, facilitated by T. bakamatsutake. Microbial functional predictions revealed a significant increase in pathways associated with sugar and fat catabolism within the fungal and bacterial communities of shiro. The relative genetic abundance of carboxylesterase and gibberellin 2-beta-dioxygenase in the fungal community was significantly increased, which suggested a potential symbiotic relationship between T. bakamatsutake and Q. mongolica. These findings elucidate the microbial community and relevant symbiotic environment to better understand the relationship between T. bakamatsutake and Q. mongolica.
ESTHER : Guo_2024_Front.Microbiol_15_1361117
PubMedSearch : Guo_2024_Front.Microbiol_15_1361117
PubMedID: 38601932

Title : Rapid screening of acetylcholinesterase active contaminants in water: A solid phase microextraction-based ligand fishing approach - Huang_2024_Chemosphere_356_141976
Author(s) : Huang Z , He L , Li H , Zhao J , Chen T , Feng Z , Li Y , You J
Ref : Chemosphere , 356 :141976 , 2024
Abstract : Effect-directed analysis (EDA) has been increasingly used for screening toxic contaminants in the environment, but conventional EDA procedures are often time-consuming and labor-extensive. This challenges the use of EDA for toxicant identification in the scenarios when quick answers are demanded. Herein, a solid phase microextraction ligand fishing (SPME-LF) strategy has been proposed as a rapid EDA approach for identifying acetylcholinesterase (AChE) active compounds in water. The feasibility of ligand fishing techniques for screening AChE active chemicals from environmental mixtures was first verified by a membrane separation method. Then, SPME fibers were prepared through self-assembly of boronic acid groups with AChE via co-bonding and applied for SPME-LF. As AChE coated SPME fibers selectively enriched AChE-active compounds from water, comparing sorbing compounds by the SPME fibers with and without AChE coating can quickly distinguish AChE toxicants in mixtures. Compared with conventional EDA, SPME-LF does not require repeating sample separations and bioassays, endowing SPME-LF with the merits of low-cost, labor-saving, and user-friendly. It is believed that cost-efficient and easy-to-use SPME-LF strategy can potentially be a rapid EDA method for screening receptor-specific toxicants in aquatic environment, especially applicable in time-sensitive screening.
ESTHER : Huang_2024_Chemosphere_356_141976
PubMedSearch : Huang_2024_Chemosphere_356_141976
PubMedID: 38608773

Title : ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque - Zhang_2024_J.Adv.Res__
Author(s) : Zhang Y , Yan C , Dong Y , Zhao J , Yang X , Deng Y , Su L , Yin J , Sun F , Feng Y
Ref : J Adv Res , : , 2024
Abstract : INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin alphavbeta3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin alphavbeta3 for atherosclerosis progression. METHODS: Ldlr(-/-) mice on a high-fat diet and ApoE(-/-) mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE(-/-) mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3(-/-)ApoE(-/-) mice and ApoE(-/-) littermates. THP-1 cells were exposed to 0 or 50 microg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin beta3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68(+) macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG(+) cells were identified in plaque of gene transferred ApoE(-/-) mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1beta and tumour necrosis factor-alpha in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin beta3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-kappaB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.
ESTHER : Zhang_2024_J.Adv.Res__
PubMedSearch : Zhang_2024_J.Adv.Res__
PubMedID: 38740260

Title : Acaricidal activities of paeonol from Moutan Cortex, dried bark of Paeonia suffruticosa, against the grain pest mite Aleuroglyphus ovatus (Acari: Acaridae) - Zou_2023_Exp.Appl.Acarol__
Author(s) : Zou M , Xue Q , Teng Q , Zhang Q , Liu T , Li Y , Zhao J
Ref : Exp Appl Acarol , : , 2023
Abstract : Aleuroglyphus ovatus (Acari: Acaridae) is a major pest mite of stored grains that is distributed worldwide. Paeonol, a phenolic component of the essential oil extracted from the Chinese herb Paeonia moutan, possesses a range of biological activities, including antiviral, antifungal and acaricidal activity. This study investigated the bioactivity of paeonol against A. ovatus and its effect on the activity of detoxification enzymes. The bioactivity of paeonol against A. ovatus was determined by contact, fumigation and repellency bioassays, and the mechanism was preliminarily explored via morphological observation of the color changes of mite epidermis and determination of the changing trend of some important enzymes associated with acaricidal efficacy in the mites. The results showed that the median lethal concentration (LC(50)) in the contact and fumigation bioassays was 9.832 microg/cm(2) and 14.827 microg/cm(3), respectively, and the acaricidal activity of paeonol was higher under direct contact than under fumigation. Dynamic symptomatology studies registered typical neurotoxicity symptoms including excitation, convulsion and paralysis in A. ovatus treated with paeonol. The enzyme activity of catalase (CAT), nitric oxide synthase (NOS) and glutathione-S-transferase (GST) was higher, whereas the activity of superoxide dismutase (SOD) and acetylcholinesterase (AChE) was lower, compared to the control group. CAT, NOS and GST were activated, whereas SOD and AChE activities were inhibited after paeonol intervention. Our findings suggest paeonol has potent acaricidal activity against A. ovatus and thus may be used as an agent to control the stored-product mite A. ovatus.
ESTHER : Zou_2023_Exp.Appl.Acarol__
PubMedSearch : Zou_2023_Exp.Appl.Acarol__
PubMedID: 37979065

Title : Sex differences in hippocampal beta-amyloid accumulation in the triple-transgenic mouse model of Alzheimer's disease and the potential role of local estrogens - Hu_2023_Front.Neurosci_17_1117584
Author(s) : Hu YT , Chen XL , Zhang YN , McGurran H , Stormmesand J , Breeuwsma N , Sluiter A , Zhao J , Swaab D , Bao AM
Ref : Front Neurosci , 17 :1117584 , 2023
Abstract : INTRODUCTION: Epidemiological studies show that women have a higher prevalence of Alzheimer's disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1 (M146V) , APP (Swe) , and Tau (P301L) show sex differences in beta-amyloid (Abeta) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17beta-estradiol (E2) may regulate the expression of EGR1 and AChE. METHODS: We first sacrificed male and female 3xTg-AD mice at 3-4, 7-8, and 11-12 months and measured the levels of Abeta, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Abeta and intracellular EGR1 and AChE. RESULTS: Female 3xTg-AD mice had higher levels of Abeta compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Abeta and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Abeta(l-42) was significantly decreased while intracellular EGR1 and AChE expression were elevated. DISCUSSION: This data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Ap. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Abeta(1-42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels.
ESTHER : Hu_2023_Front.Neurosci_17_1117584
PubMedSearch : Hu_2023_Front.Neurosci_17_1117584
PubMedID: 36968493

Title : Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase - Wang_2023_Foods_12_
Author(s) : Wang Y , Sun J , Zhang M , Pan K , Liu T , Zhang T , Luo X , Zhao J , Li Z
Ref : Foods , 12 : , 2023
Abstract : Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.
ESTHER : Wang_2023_Foods_12_
PubMedSearch : Wang_2023_Foods_12_
PubMedID: 36673508

Title : Identification of Potent and Selective Acetylcholinesterase\/Butyrylcholinesterase Inhibitors by Virtual Screening - Xu_2023_J.Chem.Inf.Model__
Author(s) : Xu T , Li S , Li AJ , Zhao J , Sakamuru S , Huang W , Xia M , Huang R
Ref : J Chem Inf Model , : , 2023
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play important roles in human neurodegenerative disorders such as Alzheimer's disease. In this study, machine learning methods were applied to develop quantitative structure-activity relationship models for the prediction of novel AChE and BChE inhibitors based on data from quantitative high-throughput screening assays. The models were used to virtually screen an in-house collection of -360K compounds. The optimal models achieved good performance with area under the receiver operating characteristic curve values ranging from 0.83 +/- 0.03 to 0.87 +/- 0.01 for the prediction of AChE/BChE inhibition activity and selectivity. Experimental validation showed that the best-performing models increased the assay hit rate by several folds. We identified 88 novel AChE and 126 novel BChE inhibitors, 25% (AChE) and 53% (BChE) of which showed potent inhibitory effects (IC(50) < 5 microM). In addition, structure-activity relationship analysis of the BChE inhibitors revealed scaffolds for chemistry design and optimization. In conclusion, machine learning models were shown to efficiently identify potent and selective inhibitors against AChE and BChE and novel structural series for further design and development of potential therapeutics against neurodegenerative disorders.
ESTHER : Xu_2023_J.Chem.Inf.Model__
PubMedSearch : Xu_2023_J.Chem.Inf.Model__
PubMedID: 37011147

Title : Degradation of poly(butylene adipate-co-terephthalate) films by Thermobifida fusca FXJ-1 isolated from compost - Jia_2023_J.Hazard.Mater_441_129958
Author(s) : Jia X , Zhao K , Zhao J , Lin C , Zhang H , Chen L , Chen J , Fang Y
Ref : J Hazard Mater , 441 :129958 , 2023
Abstract : In recent years, Poly(butylene adipate-co-terephthalate) (PBAT) films were wildly used due to its biodegradable properties. However, there are few reports of strains that can high efficiently degrade PBAT. Thermobifida fusca FXJ-1, a thermophilic actinomycete, was screened and identified from compost. FXJ-1 can efficiently degrade PBAT at 55C in MSM medium. The degradation rates of the pure PBAT film (PF), PBAT film used for mulching on agricultural fields (PAF), and PBAT-PLA-ST film (PPSF) were 82.871.01%, 87.832.00% and 52.530.54%, respectively, after nine days of incubation in MSM medium. Cracking areas were monitored uniformly distributed on the surfaces of three kinds of PBAT-based films after treatment with FXJ-1 using scanning electron microscopy. The LC-MS results showed that PBAT might be degraded into adipic acid, terephthalic acid, butylene adipate, butylene terephthalate and butylene adipate-co-terephthalate, and these products are involved in the cleavage of ester bonds. We also found that amylase produced by FXJ-1 played an important role in the degradation of PPSF. FXJ-1 also showed an efficient PBAT-based films degradation ability in simulating compost environment, which implied its potential application in PBAT and starch-based film degradation by industrial composting.
ESTHER : Jia_2023_J.Hazard.Mater_441_129958
PubMedSearch : Jia_2023_J.Hazard.Mater_441_129958
PubMedID: 36122523

Title : Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial - Rosenson_2023_Nat.Med__
Author(s) : Rosenson RS , Gaudet D , Ballantyne CM , Baum SJ , Bergeron J , Kershaw EE , Moriarty PM , Rubba P , Whitcomb DC , Banerjee P , Gewitz A , Gonzaga-Jauregui C , McGinniss J , Ponda MP , Pordy R , Zhao J , Rader DJ
Ref : Nat Med , : , 2023
Abstract : Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg(-1) or placebo every 4 weeks over a 12-week double-blind treatment period, followed by a 12-week single-blind treatment period. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3. Evinacumab reduced triglycerides in cohort 3 by a mean (s.e.m.) of -27.1% (37.4) (95% confidence interval -71.2 to 84.6), but the prespecified primary end point was not met. No notable differences in adverse events between evinacumab and placebo treatment groups were seen during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG. Trial registration number: ClinicalTrials.gov NCT03452228 .
ESTHER : Rosenson_2023_Nat.Med__
PubMedSearch : Rosenson_2023_Nat.Med__
PubMedID: 36879129
Gene_locus related to this paper: human-LPL

Title : Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial - Ji_2023_Diabetes.Obes.Metab_25_3671
Author(s) : Ji L , Lu J , Gao L , Ying C , Sun J , Han J , Zhao W , Gao Y , Wang K , Zheng X , Xie D , Ding J , Zhao J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3671 , 2023
Abstract : AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedID: 37661308

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : Synergism of Feeding and Digestion Regulated by the Neuropeptide F System in Ostrinia furnacalis Larvae - Zhao_2023_Cells_12_
Author(s) : Zhao J , Song Y , Jiang X , He L , Wei L , Zhao Z
Ref : Cells , 12 : , 2023
Abstract : Feeding is crucial for the growth and survival of animals, including humans, but relatively little is known about how it is regulated. Here, we show that larval feeding in Ostrinia furnacalis is regulated by neuropeptide F (NPF, the homologous peptide of mammalian NPY) via the insulin signalling pathway in the midgut. Furthermore, the genes pi3k and mtor in the insulin pathway positively regulate alpha-amylase and lipase of the midgut by recruiting the transcription factors c-Myc and PPARgamma for binding to the promotors of these two enzymes. Importantly, we find that the feeding behaviour and the digestive system of midgut in O. furnacalis larvae are closely related and interactive in that knocking down alpha-amylase or lipase induces a reduction in larval feeding, while food-deprived larvae lead to fewer expressions of alpha-amylase and lipase. Importantly, it is the gut NPF that regulates the alpha-amylase and lipase, while variations of alpha-amylase and lipase may feed back to the brain NPF. This current study reveals a molecular feedback mechanism between feeding behaviour and the digestive system that is regulated by the conserved NPF via insulin signalling systems in the midgut of O. furnacalis larvae.
ESTHER : Zhao_2023_Cells_12_
PubMedSearch : Zhao_2023_Cells_12_
PubMedID: 36611986

Title : ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models - Chen_2023_J.Inflamm.Res_16_6361
Author(s) : Chen Y , Du H , Wang X , Li B , Chen X , Yang X , Zhao C , Zhao J
Ref : J Inflamm Res , 16 :6361 , 2023
Abstract : INTRODUCTION: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM. METHODS: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene. RESULTS: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments. DISCUSSION: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.
ESTHER : Chen_2023_J.Inflamm.Res_16_6361
PubMedSearch : Chen_2023_J.Inflamm.Res_16_6361
PubMedID: 38161353

Title : Impacts of exposure to nanopolystyrene and\/or chrysene at ambient concentrations on neurotoxicity in Siniperca chuatsi - Chen_2023_Chemosphere_340_139830
Author(s) : Chen T , Jiang H , Shen Y , Cui T , Yang Z , Liu Y , Zhao J , Chen X
Ref : Chemosphere , 340 :139830 , 2023
Abstract : Health risks caused by widespread environmental pollutants such as nanopolystyrene (NP) and chrysene (CHR) in aquatic ecosystems have aroused considerable concern. The present study established juvenile Mandarin fish (Siniperca chuatsi) models of NP and/or CHR exposure at ambient concentrations for 21 days to systematically investigate the underlying neurotoxicity mechanisms. The results showed that single and combined exposure to NP and CHR not only reduced the density of small neuronal cells in the grey matter layer of the optic tectum, but also induced brain oxidative stress according to physiological parameters including CAT, GSH-Px, SOD, T-AOC, and MDA. The co-exposure alleviated the histopathological damage, compared to NP and CHR single exposure group. These results indicate that NP and/or CHR causes neurotoxicity in S. chuatsi, in accordance with decreased acetylcholinesterase activity and altered expression of several marker genes of nervous system functions and development including c-fos, shha, elavl3, and mbpa. Transcriptomics analysis was performed to further investigate the potential molecular mechanisms of neurotoxicity. We propose that single NP and co-exposure induced oxidative stress activates MMP, which degrades tight junction proteins according to decreased expression of claudin, JAM, caveolin and TJP, ultimately damaging the integrity of the blood-brain barrier in S. chuatsi. Remarkably, the co-exposure exacerbated the blood-brain barrier disruption. More importantly, single NP and co-exposure induced neuronal apoptosis mainly activates the expression of apoptosis-related genes through the death receptor apoptosis pathway, while CHR acted through both death receptor apoptosis and endoplasmic reticulum apoptosis pathways. Additionally, subchronic CHR exposure caused neuroinflammation, supported by activation of TNF/NF-kappaB and JAK-STAT signaling pathways via targeting-related genes, while the co-exposure greatly alleviated the neuroinflammation. Collectively, our findings illuminate the underlying neurotoxicity molecular mechanisms of NP and/or CHR exposure on aquatic organisms.
ESTHER : Chen_2023_Chemosphere_340_139830
PubMedSearch : Chen_2023_Chemosphere_340_139830
PubMedID: 37597625

Title : Neurotoxic effects of chloroquine and its main transformation product formed after chlorination - Hu_2023_Sci.Total.Environ__168043
Author(s) : Hu S , Zhao J , Fang S , Guo K , Qi W , Liu H
Ref : Sci Total Environ , :168043 , 2023
Abstract : Pharmaceutical transformation products (TPs) generated during wastewater treatment have become an environmental concern. However, there is limited understanding regarding the TPs produced from pharmaceuticals during wastewater treatment. In this study, chloroquine (CQ), which was extensively used for treating coronavirus disease-19 (COVID-19) infections during the pandemic, was selected for research. We identified and fractionated the main TP produced from CQ during chlorine disinfection and investigated the neurotoxic effects of CQ and its main TP on zebrafish (Danio rerio) embryos. Halogenated TP353 was observed as one of the main TPs produced from CQ during chlorine disinfection. Zebrafish embryos test revealed that TP353 caused higher neurotoxicity in zebrafish larvae, as compared to the CQ, and that was accompanied by significantly decreased expression levels of the genes related to central nervous system development (e.g., gfap, syn2a, and elavl3), inhibited activity of acetylcholinesterase (AChE), reduced GFP fluorescence intensity of motor neuron axons in transgenic larvae (hb9-GFP), and reduced total swimming distance and swimming velocity of larvae during light-dark transition stimulation. The results of this study can potentially be utilized as a theoretical reference for future evaluations of environmental risks associated with CQ and its related TPs. This work presents a methodology for assessing the environmental hazards linked to the discharge of pharmaceutical TPs after wastewater treatment.
ESTHER : Hu_2023_Sci.Total.Environ__168043
PubMedSearch : Hu_2023_Sci.Total.Environ__168043
PubMedID: 37898196

Title : Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease - Yang_2023_Bioorg.Chem_133_106432
Author(s) : Yang F , Zhao J , Chen G , Han H , Hu S , Wang N , Wang J , Chen Y , Zhou Z , Dai B , Hou Y , Liu Y
Ref : Bioorg Chem , 133 :106432 , 2023
Abstract : Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca(2+) homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca(2+) release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC(50) = 0.162 microM) and AChE (inhibition (%) = 93.5, IC(50) = 0.372 microM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD.
ESTHER : Yang_2023_Bioorg.Chem_133_106432
PubMedSearch : Yang_2023_Bioorg.Chem_133_106432
PubMedID: 36841050

Title : Chemical Composition, In Vitro Antioxidant Activities, and Inhibitory Effects of the Acetylcholinesterase of Liparis nervosa (Thunb.) Lindl. Essential Oil - Zhao_2023_Biomolecules_13_
Author(s) : Zhao J , Xu Z , Gao P , Liu X
Ref : Biomolecules , 13 : , 2023
Abstract : The present study aimed to investigate the essential oil composition of Liparis nervosa (Thunb.) Lindl., grown in China, and to determine its antioxidant and inhibitory effects on acetylcholinesterase. The essential oil was obtained by hydrodistillation, and the chemical compounds were analyzed by GC-MS and GC-FID. We used 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing assay power (FRAP) to evaluate the antioxidant activity. The anti-acetylcholinesterase activity of the essential oil was also examined. Sixty-seven compounds were identified, representing 98.50 % of the total essential oil, which was shown to be rich in methyl (9E,11E)-octadeca-9,11-dienoate (31.69%), n-hexadecanoic acid (15.08%), isopropyl palmitate (12.44%), propyl tetradecanoate (7.20%), tetradecanoic acid (4.01%), 17-octadecynoic acid (3.71%), and pentacosane (2.24%). Its antioxidant ability was analyzed via ABTS (IC(50) = 721.95 +/- 9.93 microg/mL), DPPH scavenging capacity (IC(50) > 10,000 microg/mL), and the FRAP method (Trolox equivalent antioxidant concentration 39.64 +/- 3.38 microM/g). Acetylcholinesterase inhibition effects were evaluated and had an IC(50) value of 51.96 +/- 14.26 microg/mL. The results show that this essential oil has interesting biological potential, encouraging further investigations, especially regarding the mechanisms of action of its antioxidant and anti-acetylcholinesterase activity. This is the first time that the chemical composition, antioxidant activity, and acetylcholinesterase inhibition effects of essential oil from L. nervosa have been studied.
ESTHER : Zhao_2023_Biomolecules_13_
PubMedSearch : Zhao_2023_Biomolecules_13_
PubMedID: 37509125

Title : Expression and characterization of a novel lipase from Bacillus licheniformis NCU CS-5 for application in enhancing fatty acids flavor release for low-fat cheeses - Zhao_2022_Food.Chem_368_130868
Author(s) : Zhao J , Ma M , Yan X , Zhang G , Xia J , Zeng G , Tian W , Bao X , Zeng Z , Yu P , Gong D
Ref : Food Chem , 368 :130868 , 2022
Abstract : A novel lipase from Bacillus licheniformis NCU CS-5 was expressed in different Escherichia coli cells. The recombinant enzyme achieved a high activity (161.74 U/mL) with protein concentration of 0.27 mg/mL under optimal conditions at the large-scale expression of 12 h. The recombinant lipase showed optimal activity at 40 degC and pH 10.0, and maintained more than 80% relative activity after 96 h of incubation at pH 9.0-10.0. This typical alkaline lipase was activated under medium temperature conditions (30 and 45 degC for 96 h). The lipase exhibited a degree of adaptability in various organic solvents and metal ions, and showed high specificity towards triglycerides with short and medium chain fatty acids. Among different substrates, the lipase showed the strongest binding affinity towards pNPP (Km = 0.674 mM, Vmax = 950.196 microM/min). In the experiments of its application in enhancing fatty acids flavor release for low-fat cheeses, the lipase was found to hydrolyze cheeses and mainly increase the contents of butyric acid, hexanoic acid, caprylic acid and decanoic acid. The results from NMR and GC provided the possibility of enhancing fatty acids flavor released from low-fat cheeses by the lipolysis method.
ESTHER : Zhao_2022_Food.Chem_368_130868
PubMedSearch : Zhao_2022_Food.Chem_368_130868
PubMedID: 34438173
Gene_locus related to this paper: bacld-q65hr4

Title : Immobilization of lipase on beta-cyclodextrin grafted and aminopropyl-functionalized chitosan\/Fe(3)O(4) magnetic nanocomposites: An innovative approach to fruity flavor esters esterification - Zhao_2022_Food.Chem_366_130616
Author(s) : Zhao J , Ma M , Yan X , Wan D , Zeng Z , Yu P , Gong D
Ref : Food Chem , 366 :130616 , 2022
Abstract : The lipase from Bacillus licheniformis NCU CS-5 was immobilized onto beta-cyclodextrin (CD) grafted and aminopropyl-functionalized chitosan-coated Fe(3)O(4) magnetic nanocomposites (Fe(3)O(4)-CTS-APTES-GA-beta-CD). Fourier transform infrared spectroscopy, thermogravimetry analysis, X-ray diffraction, scanning electron microscopy and transmission electron microscopy showed that not only the functionalized magnetic nanoparticles were synthesized but also the immobilized lipase was successfully produced. The immobilized lipase exhibited higher optimal pH value (10.5) and temperature (60 degC) than the free lipase. The pH and thermal stabilities of the immobilized lipase were improved significantly compared to the free lipase. The immobilized lipase remained more than 80% of the relative activity at temperature of 60 degC and pH 12.0. The immobilized lipase also remained over 80% of its relative activity after 28 days of storage and 15 cycles of application. The application of the immobilized lipase in esterification of isoamyl acetate and pentyl valerate showed that maximum esterification efficiency was achieved in n-hexane having 68.0% and 89.2% respectively. Therefore, these results indicated that the Fe(3)O(4)-CTS-APTES-GA-beta-CD nanoparticles are novel carriers for immobilizing enzyme, and the immobilized lipase can be used as an innovative green approach to the synthesis of fruity flavor esters in food industry.
ESTHER : Zhao_2022_Food.Chem_366_130616
PubMedSearch : Zhao_2022_Food.Chem_366_130616
PubMedID: 34311240
Gene_locus related to this paper: bacld-q65hr4

Title : Neuronal STAT3\/HIF-1alpha\/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A - Jin_2022_Theranostics_12_3196
Author(s) : Jin W , Zhao J , Yang E , Wang Y , Wang Q , Wu Y , Tong F , Tan Y , Zhou J , Kang C
Ref : Theranostics , 12 :3196 , 2022
Abstract : Ischemic stroke is an acute and severe neurological disease with high mortality and disability rates worldwide. Polymerase I and transcript release factor (PTRF) plays a pivotal role in regulating cellular senescence, glucose intolerance, lipid metabolism, and mitochondrial bioenergetics, but its mechanism, characteristics, and functions in neuronal cells following the cerebral ischemia-reperfusion (I/R) injury remain to be determined. Methods: Transcription factor motif analysis, chromatin immunoprecipitation (ChIP), luciferase and co-Immunoprecipitation (co-IP) assays were performed to investigate the mechanisms of PTRF in neuronal cells after I/R injury. Lentiviral-sgRNA against PTRF gene was introduced to HT22 cells, and adeno-associated virus (AAV) encoding a human synapsin (hSyn) promoter-driven construct was transduced a short hairpin RNA (shRNA) against PTRF mRNA in primary neuronal cells and the cortex of the cerebral I/R mice for investigating the role of PTRF in neuronal damage and PLA2G4A change induced by the cerebral I/R injury. Results: Here, we reported that neuronal PTRF was remarkably increased in the cerebral penumbra after I/R injury, and HIF-1alpha and STAT3 regulated the I/R-dependent expression of PTRF via binding to its promoter in neuronal cells. Moreover, overexpression of neuronal PTRF enhanced the activity and stability of PLA2G4A by decreasing its proteasome-mediated degradation pathway. Subsequently, PTRF promoted reprogramming of lipid metabolism and altered mitochondrial bioenergetics, which could lead to oxidative damage, involving autophagy, lipid peroxidation, and ferroptosis via PLA2G4A in neuronal cells. Furthermore, inhibition of neuronal PTRF/PLA2G4A-axis markedly reduced the neurological deficits, cerebral infarct volumes, and mortality rates in the mice following cerebral I/R injury. Conclusion: Our results thus identify that the STAT3/HIF-1alpha/PTRF-axis in neurons, aggravating cerebral I/R injury by regulating the activity and stability of PLA2G4A, might be a novel therapeutic target for ischemic stroke.
ESTHER : Jin_2022_Theranostics_12_3196
PubMedSearch : Jin_2022_Theranostics_12_3196
PubMedID: 35547748

Title : Molecular mechanism of LIP05 derived from Monascus purpureus YJX-8 for synthesizing fatty acid ethyl esters under aqueous phase - Zhao_2022_Front.Microbiol_13_1107104
Author(s) : Zhao J , Xu Y , Lu H , Zhao D , Zheng J , Lin M , Liang X , Ding Z , Dong W , Yang M , Li W , Zhang C , Sun B , Li X
Ref : Front Microbiol , 13 :1107104 , 2022
Abstract : Fatty acid ethyl esters are important flavor chemicals in strong-flavor Baijiu. Monascus purpureus YJX-8 is recognized as an important microorganism for ester synthesis in the fermentation process. Enzyme LIP05 from YJX-8 can efficiently catalyze the synthesis of fatty acid ethyl esters under aqueous phase, but the key catalytic sites affecting esterification were unclear. The present work combined homology modeling, molecular dynamics simulation, molecular docking and site-directed mutation to analyze the catalytic mechanism of LIP05. Protein structure modeling indicated LIP05 belonged to alpha/beta fold hydrolase, contained a lid domain and a core catalytic pocket with conserved catalytic triad Ser150-His215-Asp202, and the oxyanion hole composed of Gly73 and Thr74. Ile30 and Leu37 of the lid domain were found to affect substrate specificity. The Pi-bond stacking between Tyr116 and Tyr149 played an important role in stabilizing the catalytic active center of LIP05. Tyr116 and Ile204 determined the substrate spectrum by composing the substrate-entrance channel. Residues Leu83, Ile204, Ile211 and Leu216 were involved in forming the hydrophobic substrate-binding pocket through steric hindrance and hydrophobic interaction. The catalytic mechanism for esterification in aqueous phase of LIP05 was proposed and provided a reference for clarifying the synthesis of fatty acid ethyl esters during the fermentation process of strong-flavor Baijiu.
ESTHER : Zhao_2022_Front.Microbiol_13_1107104
PubMedSearch : Zhao_2022_Front.Microbiol_13_1107104
PubMedID: 36713181

Title : Green synthesis of polydopamine functionalized magnetic mesoporous biochar for lipase immobilization and its application in interesterification for novel structured lipids production - Zhao_2022_Food.Chem_379_132148
Author(s) : Zhao J , Ma M , Yan X , Zhang G , Xia J , Zeng Z , Yu P , Deng Q , Gong D
Ref : Food Chem , 379 :132148 , 2022
Abstract : In this study, the polydopamine functionalized magnetic mesoporous biochar (MPCB-DA) was prepared for immobilization of Bacillus licheniformis lipase via covalent immobilization. Under optimized immobilization conditions, the maximum immobilization yield, efficiency and immobilized lipase amount were found to be 45%, 54% and 36.9 mg/g, respectively. The immobilized lipase, MPCB-DA-Lipase showed good thermal stability and alkali resistance. The MPCB-DA-Lipase retained 56% initial activity after 10 reuse cycles, with more than 85% relative activity after 70 days' storage at 4 or 25 degreesC. The MPCB-DA-Lipase was efficiently applied in the interesterification of Cinnamomum camphora seed kernel oil and perilla seed oil, with maximum interesterification efficiency of 46%. The produced structured lipids belong to the S(2)U and U(2)S triacylglycerols, a novel medium-and long-chain triacylglycerol. These results demonstrated that the MPCB-DA-Lipase may be used as an efficient biocatalyst in lipid processing applications of food industries.
ESTHER : Zhao_2022_Food.Chem_379_132148
PubMedSearch : Zhao_2022_Food.Chem_379_132148
PubMedID: 35074745

Title : The yin and yang of intracellular delivery of amphipathic optical probes using n-butyl charge masking - Agarwal_2022_Chem.Commun.(Camb)__
Author(s) : Agarwal HK , Janicek R , Zhao J , Sambath K , Egger M , Niggli E , Ellis-Davies GCR
Ref : Chem Commun (Camb) , : , 2022
Abstract : Monitoring and manipulation of ionized intracellular calcium concentrations within intact, living cells using optical probes with organic chromophores is a core method for cell physiology. Since all these probes have multiple negative charges, they must be smuggled through the plasma membrane in a transiently neutral form, with intracellular esterases used to deprotect the masked anions. Here we explore the ability of the synthetically easily accessible n-butyl ester protecting group to deliver amphipathic cargoes to the cytosol. We show that the size of the caging chromophore conditions the ability of intracellular probe delivery and esterase charge unmasking.
ESTHER : Agarwal_2022_Chem.Commun.(Camb)__
PubMedSearch : Agarwal_2022_Chem.Commun.(Camb)__
PubMedID: 35112125

Title : The Comparative Analysis of Genomic Diversity and Genes Involved in Carbohydrate Metabolism of Eighty-Eight Bifidobacterium pseudocatenulatum Isolates from Different Niches of China - Lin_2022_Nutrients_14_
Author(s) : Lin G , Liu Q , Wang L , Li H , Zhao J , Zhang H , Wang G , Chen W
Ref : Nutrients , 14 : , 2022
Abstract : Eighty-eight Bifidobacterium pseudocatenulatum strains, which were isolated from human, chicken and cow fecal samples from different niches of China, were compared genomically in this study to evaluate their diversity. It was found that B. pseudocatenulatum displayed a closed pan-genome, including abundant glycoside hydrolase families of the carbohydrate active enzyme (CAZy). A total of 30 kinds of glycoside hydrolases (GHs), 14 kinds of glycosyl transferases (GTs), 13 kinds of carbohydrate-binding modules (CBMs), 6 kinds of carbohydrate-esterases (CEs), and 2 kinds of auxiliary activities (AAs) gene families were identified across the genomes of the 88 B. pseudocatenulatum strains. Specifically, this showed that significant differences were also present in the number of 10 carbohydrate-active enzyme gene families (GT51, GH13_32, GH26, GH42, GH121, GH3, AA3, CBM46, CE2, and CE6) among the strains derived from the hosts of different age groups, particularly between strains from infants and those from other human age groups. Twelve different individuals of B. pseudocatenulatum from four main clusters were selected for further study to reveal the genetic diversity of carbohydrate metabolism-related genes within the same phylogenetics. The animal experiment showed that 3 weeks of oral administration and 1 week after cessation of administration of these strains did not markedly alter the serum routine inflammatory indicators in mice. Furthermore, the administration of these strains did not significantly cause adverse changes in the gut microbiota, as indicated by the alpha- and beta-diversity indexes, relative to the control group (normal diet). Beyond that, FAHBZ9L5 significantly increased the abundance of B. pseudocatenulatum after 3 weeks and significantly increased the abundance of acetic acid and butyric acid in the host's intestinal tract 3 and 4 weeks after the first administration, respectively, compared with the control group. Corresponding to this, comparative genomic analyses of 12 B. pseudocatenulatum suggest that FAHBZ9L5-specific genes were rich in ABC transporters and carbohydrate esterase. Combining the results of comparative genomics analyses and animal experiment, it is suggested that the strains containing certain gene clusters contribute to another competitive growth advantage of B. pseudocatenulatum, which facilitates its intestinal carbohydrate metabolism in a host.
ESTHER : Lin_2022_Nutrients_14_
PubMedSearch : Lin_2022_Nutrients_14_
PubMedID: 35684146

Title : Acetylcholinesterase Inhibition Assays for High-Throughput Screening - Li_2022_Methods.Mol.Biol_2474_47
Author(s) : Li S , Li AJ , Zhao J , Santillo MF , Xia M
Ref : Methods Mol Biol , 2474 :47 , 2022
Abstract : Acetylcholinesterase (AChE) hydrolyzes acetylcholine (ACh), a vital neurotransmitter that regulates muscle movement and brain function, including memory, attention, and learning. Inhibition of AChE activity can cause a variety of adverse health effects and toxicity. Identifying AChE inhibitors quickly and efficiently warrants developing AChE inhibition assays in a quantitative, high-throughput screening (qHTS) platform. In this chapter, protocols for multiple homogenous AChE inhibition assays used in a qHTS system are provided. These AChE inhibition assays include a (1) human neuroblastoma (SH-SY5Y) cell-based assay with fluorescence or colorimetric detection; (2) human recombinant AChE with fluorescence or colorimetric detection; and (3) combination of human recombinant AChE and liver microsomes with colorimetric detection, which enables detection of test compounds requiring metabolic activation to become AChE inhibitors. Together, these AChE assays can help identify, prioritize, and predict chemical hazards in large compound libraries using qHTS systems.
ESTHER : Li_2022_Methods.Mol.Biol_2474_47
PubMedSearch : Li_2022_Methods.Mol.Biol_2474_47
PubMedID: 35294755

Title : Genome-Wide Detection of Copy Number Variations and Evaluation of Candidate Copy Number Polymorphism Genes Associated With Complex Traits of Pigs - Zhang_2022_Front.Vet.Sci_9_909039
Author(s) : Zhang C , Zhao J , Guo Y , Xu Q , Liu M , Cheng M , Chao X , Schinckel AP , Zhou B
Ref : Front Vet Sci , 9 :909039 , 2022
Abstract : Copy number variation (CNV) has been considered to be an important source of genetic variation for important phenotypic traits of livestock. In this study, we performed whole-genome CNV detection on Suhuai (SH) (n = 23), Chinese Min Zhu (MZ) (n = 11), and Large White (LW) (n = 12) pigs based on next-generation sequencing data. The copy number variation regions (CNVRs) were annotated and analyzed, and 10,885, 10,836, and 10,917 CNVRs were detected in LW, MZ, and SH pigs, respectively. Some CNVRs have been randomly selected for verification of the variation type by real-time PCR. We found that SH and LW pigs are closely related, while MZ pigs are distantly related to the SH and LW pigs by CNVR-based genetic structure, PCA, V(ST), and QTL analyses. A total of 14 known genes annotated in CNVRs were unique for LW pigs. Among them, the cyclin T2 (CCNT2) is involved in cell proliferation and the cell cycle. The FA Complementation Group M (FANCM) is involved in defective DNA repair and reproductive cell development. Ten known genes annotated in 47 CNVRs were unique for MZ pigs. The genes included glycerol-3-phosphate acyltransferase 3 (GPAT3) is involved in fat synthesis and is essential to forming the glycerol triphosphate. Glutathione S-transferase mu 4 (GSTM4) gene plays an important role in detoxification. Eleven known genes annotated in 23 CNVRs were unique for SH pigs. Neuroligin 4 X-linked (NLGN4X) and Neuroligin 4 Y-linked (NLGN4Y) are involved with nerve disorders and nerve signal transmission. IgLON family member 5 (IGLON5) is related to autoimmunity and neural activities. The unique characteristics of LW, MZ, and SH pigs are related to these genes with CNV polymorphisms. These findings provide important information for the identification of candidate genes in the molecular breeding of pigs.
ESTHER : Zhang_2022_Front.Vet.Sci_9_909039
PubMedSearch : Zhang_2022_Front.Vet.Sci_9_909039
PubMedID: 35847642

Title : Sucrose promotes D53 accumulation and tillering in rice - Patil_2022_New.Phytol_234_122
Author(s) : Patil SB , Barbier FF , Zhao J , Zafar SA , Uzair M , Sun Y , Fang J , Perez-Garcia MD , Bertheloot J , Sakr S , Fichtner F , Chabikwa TG , Yuan S , Beveridge CA , Li X
Ref : New Phytol , 234 :122 , 2022
Abstract : Shoot branching is regulated by multiple signals. Previous studies have indicated that sucrose may promote shoot branching through suppressing the inhibitory effect of the hormone strigolactone (SL). However, the molecular mechanisms underlying this effect are unknown. Here, we used molecular and genetic tools to identify the molecular targets underlying the antagonistic interaction between sucrose and SL. We showed that sucrose antagonizes the suppressive action of SL on tillering in rice and on the degradation of D53, a major target of SL signalling. Sucrose inhibits the gene expression of D3, the orthologue of the Arabidopsis F-box MAX2 required for SL signalling. Overexpression of D3 antagonizes sucrose inhibition of D53 degradation and enables the SL inhibition of tillering under high sucrose. Sucrose prevents SL-induced degradation of D14, the SL receptor involved in D53 degradation. In contrast to D3, D14 overexpression enhances D53 protein levels and sucrose-induced tillering, even in the presence of SL. Our results show that sucrose inhibits SL response by affecting key components of SL signalling and, together with previous studies reporting the inhibition of SL synthesis by nitrate and phosphate, demonstrate the central role played by SLs in the regulation of plant architecture by nutrients.
ESTHER : Patil_2022_New.Phytol_234_122
PubMedSearch : Patil_2022_New.Phytol_234_122
PubMedID: 34716593

Title : Integrative assessment of biomarker responses in Mytilus galloprovincialis exposed to seawater acidification and copper ions - Qu_2022_Sci.Total.Environ_851_158146
Author(s) : Qu Y , Zhang T , Zhang R , Wang X , Zhang Q , Wang Q , Dong Z , Zhao J
Ref : Sci Total Environ , 851 :158146 , 2022
Abstract : The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 microg/L and 50 microg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered.
ESTHER : Qu_2022_Sci.Total.Environ_851_158146
PubMedSearch : Qu_2022_Sci.Total.Environ_851_158146
PubMedID: 35987231

Title : Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform - Zhao_2022_ACS.Cent.Sci_8_1424
Author(s) : Zhao J , Tang Z , Selvaraju M , Johnson KA , Douglas JT , Gao PF , Petrassi HM , Wang MZ , Wang J
Ref : ACS Cent Sci , 8 :1424 , 2022
Abstract : Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. We tested this platform on BDW568, a newly discovered type-I interferon signaling activator, and identified stimulator of interferon genes (STING) as its target and carboxylesterase 1 (CES1) to be a key metabolizing enzyme required to activate BDW568 for target engagement. The platform we present here can be a general method applicable for target identification for a wide range of small molecules that activate different signaling pathways.
ESTHER : Zhao_2022_ACS.Cent.Sci_8_1424
PubMedSearch : Zhao_2022_ACS.Cent.Sci_8_1424
PubMedID: 36313155

Title : Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia - Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
Author(s) : Wang S , Cheng Y , Shi Y , Zhao W , Gao L , Fang L , Jin X , Han X , Sun Q , Li G , Zhao J , Xu C
Ref : Front Endocrinol (Lausanne) , 13 :874608 , 2022
Abstract : BACKGROUND: Type I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis. OBJECTIVE: This study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia. METHODS: We conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium. RESULTS: Proband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 +/- 9.46% (p<0.01) and 54.60 +/- 9.03% (p<0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants. CONCLUSIONS: Two novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity.
ESTHER : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedSearch : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedID: 35923617
Gene_locus related to this paper: human-LPL

Title : Tuning the Properties of Ester-Based Degradable Polymers by Inserting Epoxides into Poly(E-caprolactone) - Hu_2022_Chem.Asian.J__e202201097
Author(s) : Hu S , Liu L , Li H , Pahovnik D , Hadjichristidis N , Zhou X , Zhao J
Ref : Chem Asian J , :e202201097 , 2022
Abstract : A series of ester-ether copolymers were obtained via the reaction between alpha,omega-dihydroxyl poly(E-caprolactone) (PCL) and ethylene oxide (EO) or monosubstituted epoxides catalyzed by strong phosphazene bases. The two types of monomeric units were distributed in highly random manners due to the concurrence of epoxide ring-opening and fast transesterification reactions. The substituent of epoxide showed an interesting bidirectional effect on the enzymatic degradability of the copolymer. Compared with PCL, copolymers derived from EO exhibited enhanced hydrophilicity and decreased crystallinity which then resulted in higher degradability. For the copolymers derived from propylene oxide and 1,2-butylene oxide, the hydrophobic alkyl pendant groups also allowed lower crystallinity of the copolymers thus higher degradation rates. However, further enlarging the pendant groups by using styrene oxide or 2-ethylhexyl glycidyl ether caused a decrease in the degradation rate, which might be ascribed to the higher bulkiness hindering the contact of ester groups with lipase.
ESTHER : Hu_2022_Chem.Asian.J__e202201097
PubMedSearch : Hu_2022_Chem.Asian.J__e202201097
PubMedID: 36424185

Title : Potentially tunable ratiometric electrochemiluminescence sensing based on conjugated polymer nanoparticle for organophosphorus pesticides detection - He_2022_J.Hazard.Mater_432_128699
Author(s) : He Y , Yang G , Zhao J , Tan K , Yuan R , Chen S
Ref : J Hazard Mater , 432 :128699 , 2022
Abstract : In general, suitable double luminophores and their coreactants are necessary for constructing electrochemiluminescence (ECL) ratio strategy. However, the complexity of matching double luminophores and the stability and repeatability problem suffered by introducing exogenous coreactant would greatly limit the application of ratio detection. An original single-luminophore-based ECL ratio sensing was developed excluding any exogenous coreactants in this work. The poly [9,9-bis(3'-(N,N-dimethylamino)propyl)- 2,7-fluorene]-alt-2,7-(9,9-dioctylfluorene)] nanoparticles (PFN NPs) were explored to emit two anodic ECL signals. One centered at + 1.25 V (ECL-1) with the scanning potential of 0 ~ + 1.25 V and the other at + 1.95 V (ECL-2) with the scanning potential of 0 ~ + 1.95 V. ECL-1 showed a very strong emission without any exogenous coreactant. Importantly, hydrogen peroxide (H(2)O(2)) was able to efficiently weaken ECL-1 but strengthen ECL-2. When organophosphorus pesticides (OPs) were absent, the immobilized acetylcholinesterase-choline oxidase (AChE-ChOx) would catalyze the substrate acetylthiocholine chloride (ATCl) to produce H(2)O(2), resulting in a quenched ECL-1 and an enhanced ECL-2. With the introduction of OPs, ECL-1 increased while ECL-2 accordingly decreased as OPs prohibited production of H(2)O(2) by inhibiting activity of AChE. Highly sensitive ECL ratio detection for OPs was realized based on the change of the ratio of two signals. The dual anode emission properties of PFN NPs coupled with the opposite regulation of H(2)O(2) on the two signals paved a new avenue for potentially tunable ECL ratio sensing strategy, and showed enormous potential applications for OPs analysis.
ESTHER : He_2022_J.Hazard.Mater_432_128699
PubMedSearch : He_2022_J.Hazard.Mater_432_128699
PubMedID: 35325864

Title : Identification of Conserved and Divergent Strigolactone Receptors in Sugarcane Reveals a Key Residue Crucial for Plant Branching Control - Hu_2021_Front.Plant.Sci_12_747160
Author(s) : Hu A , Zhao Q , Chen L , Zhao J , Wang Y , Feng K , Wu L , Xie M , Zhou X , Xiao L , Ming Z , Zhang M , Yao R
Ref : Front Plant Sci , 12 :747160 , 2021
Abstract : Strigolactones (SLs) are a class of important plant hormones mainly regulating plant architecture such as branching, which is crucial for crop yield. It is valuable to study SL signaling pathway and its physiological function in sugarcane, the most important sugar crop, for further molecular breeding. Here, two putative SL receptors SsD14a/b and the interacting F-box protein SsMAX2 were identified in Saccharum spontaneum. SL induced both SsD14a and SsD14b to interact with SsMAX2 in yeast. SsD14a, but not SsD14b, could bind with AtMAX2 and AtSMXL7/SsSMXL7. Overexpression of SsD14a or SsMAX2 rescued the increased branching phenotypes of Arabidopsis thaliana d14-1 or max2-3 mutants, respectively. Moreover, the crystal structure of N-terminal truncated SsD14a was solved, with an overall structure identical to AtD14 and OsD14 in the open state, consistent with its conserved branching suppression capacity in Arabidopsis. In line with the biochemical observations, SsD14b could not completely complement in d14-1 although these two SsD14 proteins have almost identical primary sequences except for very few residues. Complement with the combination of SsD14b and SsMAX2 still failed to rescue the d14-1 max2-3 double mutant multi-branching phenotype, indicating SsD14b-AtSMXL7 complex formation is required for regulating branching. Mutagenesis analyses revealed that residue R310 at alpha10 helix of SsD14a was crucial for the binding with SsSMXL7/AtSMXL7 but not SsMAX2. The site-equivalent single-residue P304R substitution enabled SsD14b to bind with AtMAX2 and AtSMXL7/SsSMXL7 and to rescue the phenotype of d14-1 max2-3 together with SsMAX2. Moreover, this conserved Arg residue across species including rice and Arabidopsis determined the activity of SL receptors through maintaining their interaction with SMXL repressors. Taken together, our work identified conserved and divergent strigolactone receptors in sugarcane core SL signaling pathway and revealed a key residue crucial for plant branching control.
ESTHER : Hu_2021_Front.Plant.Sci_12_747160
PubMedSearch : Hu_2021_Front.Plant.Sci_12_747160
PubMedID: 34858455
Gene_locus related to this paper: 9poal-a0a0d5nt23

Title : Characterization of a novel lipase from Bacillus licheniformis NCU CS-5 for applications in detergent industry and biodegradation of 2,4-D butyl ester - Zhao_2021_Int.J.Biol.Macromol__
Author(s) : Zhao J , Liu S , Gao Y , Ma M , Yan X , Cheng D , Wan D , Zeng Z , Yu P , Gong D
Ref : Int J Biol Macromol , : , 2021
Abstract : Enzymatic degradation has become the most promising approach to degrading organic ester compounds. In this study, Bacillus licheniformis NCU CS-5 was isolated from the spoilage of Cinnamomum camphora seed kernel, and its extracellular lipase was purified, with a specific activity of 192.98 U/mg. The lipase was found to be a trimeric protein as it showed a single band of 27 kDa in SDS-PAGE and 81 kDa in Native-PAGE. It was active in a wide range of temperatures (5-55 degreesC) and pH values (6.0-9.0), and the optimal temperature and pH value were 40 degreesC and 8.0, respectively. The enzyme was active in the presence of various organic solvents, metal ions, inhibitors and surfactants. Both crude and purified lipase retained more than 80% activity after 5 h in the presence of commercial detergents, suggesting its great application potential in detergent industry. The highest activity was found to be towards medium- and long-chain fatty acids (C(6)-C(18)). Peptide mass spectrometric analysis of the purified lipase showed similarity to the lipase family of B. licheniformis. Furthermore, it degraded more than 90% 2,4-D butyl ester to its hydrolysate 2,4-D within 24 h, indicating that the novel lipase may be applied to degrade organic ester pesticides.
ESTHER : Zhao_2021_Int.J.Biol.Macromol__
PubMedSearch : Zhao_2021_Int.J.Biol.Macromol__
PubMedID: 33548313
Gene_locus related to this paper: bacld-q65hr4

Title : An efficient phthalate ester-degrading Bacillus subtilis: Degradation kinetics, metabolic pathway, and catalytic mechanism of the key enzyme - Xu_2021_Environ.Pollut_273_116461
Author(s) : Xu Y , Liu X , Zhao J , Huang H , Wu M , Li X , Li W , Sun X , Sun B
Ref : Environ Pollut , 273 :116461 , 2021
Abstract : Phthalate ester pollution in the environment and food chain is frequently reported. Microbial treatment is a green and efficient method for solving this problem. The isolation and systematic investigation of microorganisms generally recognized as safe (GRAS) will provide useful resources. A GRAS Bacillus subtilis strain, BJQ0005, was isolated from Baijiu fermentation starter and efficiently degraded phthalate esters (PAEs). The half-lives for di-isobutyl phthalate, di-butyl phthalate and di-(2-ethylhexyl) phthalate were 3.93, 4.28, and 25.49 h, respectively, from the initial amount of 10 mg per 10 mL reaction mixture, which are records using wild-type strains. Genome sequencing and metabolic intermediate analysis generated the whole metabolic pathway. Eighteen enzymes from the alpha/beta hydrolase family were expressed. Enzymes GTW28_09400 and GTW28_13725 were capable of single ester bond hydrolysis of PAEs, while GTW28_17760 hydrolyzed di-ester bonds of PAEs. Using molecular docking, a possible mechanism affecting enzymatic ester bond hydrolysis of mono-butyl phthalate was proposed of GTW28_17760. The carboxyl group generated by the first hydrolysis step interacted with histidine in the catalytic active center, which negatively affected enzymatic hydrolysis. Isolation and systematic investigation of the PAE degradation characteristics of B. subtilis will promote the green and safe treatment of PAEs in the environment and food industry.
ESTHER : Xu_2021_Environ.Pollut_273_116461
PubMedSearch : Xu_2021_Environ.Pollut_273_116461
PubMedID: 33485001
Gene_locus related to this paper: bacsu-pnbae

Title : Genome-Wide Identification of GDSL-Type Esterase\/Lipase Gene Family in Dasypyrum villosum L. Reveals That DvGELP53 Is Related to BSMV Infection - Zhang_2021_Int.J.Mol.Sci_22_
Author(s) : Zhang H , Zhang X , Zhao J , Sun L , Wang H , Zhu Y , Xiao J , Wang X
Ref : Int J Mol Sci , 22 : , 2021
Abstract : GDSL-type esterase/lipase proteins (GELPs) characterized by a conserved GDSL motif at their N-terminus belong to the lipid hydrolysis enzyme superfamily. In plants, GELPs play an important role in plant growth, development and stress response. The studies of the identification and characterization of the GELP gene family in Triticeae have not been reported. In this study, 193 DvGELPs were identified in Dasypyrum villosum and classified into 11 groups (clade A-K) by means of phylogenetic analysis. Most DvGELPs contain only one GDSL domain, only four DvGELPs contain other domains besides the GDSL domain. Gene structure analysis indicated 35.2% DvGELP genes have four introns and five exons. In the promoter regions of the identified DvGELPs, we detected 4502 putative cis-elements, which were associated with plant hormones, plant growth, environmental stress and light responsiveness. Expression profiling revealed 36, 44 and 17 DvGELPs were highly expressed in the spike, the root and the grain, respectively. Further investigation of a root-specific expressing GELP, DvGELP53, indicated it was induced by a variety of biotic and abiotic stresses. The knockdown of DvGELP53 inhibited long-distance movement of BSMV in the tissue of D. villosum. This research provides a genome-wide glimpse of the D. villosum GELP genes and hints at the participation of DvGELP53 in the interaction between virus and plants.
ESTHER : Zhang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Zhang_2021_Int.J.Mol.Sci_22_
PubMedID: 34830200

Title : Toxicologic effect and transcriptome analysis for short-term orally dosed enrofloxacin combined with two veterinary antimicrobials on rat liver - Luan_2021_Ecotoxicol.Environ.Saf_220_112398
Author(s) : Luan Y , Zhao J , Han H , Shen J , Tang S , Cheng L
Ref : Ecotoxicology & Environmental Safety , 220 :112398 , 2021
Abstract : Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg.BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.
ESTHER : Luan_2021_Ecotoxicol.Environ.Saf_220_112398
PubMedSearch : Luan_2021_Ecotoxicol.Environ.Saf_220_112398
PubMedID: 34116333

Title : Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition - Li_2021_Environ.Health.Perspect_129_47008
Author(s) : Li S , Zhao J , Huang R , Travers J , Klumpp-Thomas C , Yu W , MacKerell AD, Jr. , Sakamuru S , Ooka M , Xue F , Sipes NS , Hsieh JH , Ryan K , Simeonov A , Santillo MF , Xia M
Ref : Environmental Health Perspectives , 129 :47008 , 2021
Abstract : BACKGROUND: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents). OBJECTIVES: The objective of the current study was to identify environmental chemicals that inhibit AChE activity using in vitro and in silico models. METHODS: To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively. RESULTS: A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds. CONCLUSIONS: Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity. https://doi.org/10.1289/EHP6993.
ESTHER : Li_2021_Environ.Health.Perspect_129_47008
PubMedSearch : Li_2021_Environ.Health.Perspect_129_47008
PubMedID: 33844597

Title : Production, purification and biochemical characterisation of a novel lipase from a newly identified lipolytic bacterium Staphylococcus caprae NCU S6 - Zhao_2021_J.Enzyme.Inhib.Med.Chem_36_248
Author(s) : Zhao J , Ma M , Zeng Z , Yu P , Gong D , Deng S
Ref : J Enzyme Inhib Med Chem , 36 :248 , 2021
Abstract : A novel lipase, SCNL, was isolated from Staphylococcus caprae NCU S6 strain in the study. The lipase was purified to homogeneity with a yield of 6.13% and specific activity of 502.76 U/mg, and its molecular weight was determined to be approximately 87 kDa. SCNL maintained above 80% of its initial activity at a wide range of temperatures (20-50 degreesC) and pH values (6-11), with an optimal temperature at 40 degreesC and optimal pH at 9.0 with p-nitrophenyl palmitate as a substrate. SCNL exhibited a higher residual activity than the other staphylococcal lipases in the presence of common enzyme inhibitors and commercial detergents. The lipase activity was enhanced by organic solvents (isooctane, glycerol, DMSO and methanol) and metal ions (Na(+), Ba(2+), Ca(2+), and Mn(2+)). The Km and Vmax values of SCNL were 0.695 mM and 262.66 s(-1 )mM(-1), respectively. The enzyme showed a preference for p-NP stearate, tributyrin and canola oil. These biochemical features of SCNL suggested that it may be an excellent novel lipase candidate for industrial and biotechnological applications.
ESTHER : Zhao_2021_J.Enzyme.Inhib.Med.Chem_36_248
PubMedSearch : Zhao_2021_J.Enzyme.Inhib.Med.Chem_36_248
PubMedID: 33327795

Title : Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization - Li_2021_Int.J.Biol.Macromol_169_18
Author(s) : Li Z , Wang Y , Liu Z , Jin S , Pan K , Liu H , Liu T , Li X , Zhang C , Luo X , Song Y , Zhao J , Zhang T
Ref : Int J Biol Macromol , 169 :18 , 2021
Abstract : Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive.
ESTHER : Li_2021_Int.J.Biol.Macromol_169_18
PubMedSearch : Li_2021_Int.J.Biol.Macromol_169_18
PubMedID: 33309671
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : An amplified fluorescence polarization assay for sensitive sensing of organophosphorus pesticides via MnO(2) nanosheets - Qin_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120759
Author(s) : Qin Y , Ye G , Liang H , Li M , Zhao J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 269 :120759 , 2021
Abstract : It is highly desirable to develop a simple, efficient and sensitive strategy for organophosphorus pesticides (OPs) in both environment pollution and human health. Herein, a novel amplified fluorescence polarization (FP) biosensor was established for highly sensitive detection of OPs using MnO(2) nanosheets as the signal enhancer. In this system, OPs can suppress the activity of acetylcholinesterase (AChE) efficiently, blocking the hydrolysis reaction of acetylthiocholine (ATCh) to generate thiocholine (TCh) by AChE. TCh can lead the decomposition of MnO(2) nanosheets to manganese ions. So, without the influence of TCh, MnO(2) nanosheets can maintain its original shape and form a stable complex with FAM-DNA, which greatly enhanced the FP signal. This method can tremendously improve the sensitivity of FP with a detection limit of 0.01 ng/mL for diazinon. In addition, it was also applicable to determine other four OPs and investigate the level of diazinon in real water samples. Consequently, the proposed approach provides a new promising platform for detection of OPs and is expected to be used in application of environmental monitoring.
ESTHER : Qin_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120759
PubMedSearch : Qin_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120759
PubMedID: 34968836

Title : Bifunctional Moderator-Powered Ratiometric Electrochemiluminescence Enzymatic Biosensors for Detecting Organophosphorus Pesticides Based on Dual-Signal Combined Nanoprobes - He_2021_Anal.Chem__
Author(s) : He Y , Hu F , Zhao J , Yang G , Zhang Y , Chen S , Yuan R
Ref : Analytical Chemistry , : , 2021
Abstract : The bifunctional moderator is urgently needed in the field of ratiometric electrochemiluminescence (ECL) sensing since it can mediate simultaneously two ECL signals to conveniently realize their opposite change trend. This work designed a novel dual-signal combined nanoprobe with carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] nanoparticles (c-PFBT NPs) as the anodic ECL probe and L-cysteine capped CdS quantum dots (L-CdS QDs) as the cathodic ECL probe, which performed a dual-signal output capability without any additional coreactants. More importantly, hydrogen peroxide (H(2)O(2)) produced in situ by enzyme-catalyzed reaction was developed as a bifunctional moderator for simultaneously regulating two signals. The dual-signal combined nanoprobe (c-PFBT NPs@CdS QDs) served as the matrix to immobilize acetylcholinesterase (AChE) and choline oxidase for organophosphorus (OPs) analysis. In the absence of OPs, H(2)O(2) was produced by catalyzing the substrate acetylthiocholine (ATCl) with enzymes and it quenched the anodic ECL signal from c-PFBT NPs and simultaneously promoted the cathodic ECL signal from L-CdS QDs. When OPs was present, the activity of AChE was inhibited, the anodic signal would increase, and the cathodic signal would accordingly decrease. The integration of the bifunctional moderator H(2)O(2) and dual-signal combined nanoprobe c-PFBT NPs@CdS QDs not only provides an attractive ECL platform for enzymatic sensing involving the generation or consumption of H(2)O(2) but also paves a new pathway for other ratiometric ECL systems involving enzyme catalytic amplification for detecting antigens, antibodies, DNA, RNA, etc.
ESTHER : He_2021_Anal.Chem__
PubMedSearch : He_2021_Anal.Chem__
PubMedID: 34133127

Title : Effect of Tannic Acid on Nutrition and Activities of Detoxification Enzymes and Acetylcholinesterase of the Fall Webworm (Lepidoptera: Arctiidae) - Yuan_2020_J.Insect.Sci_20_
Author(s) : Yuan Y , Li L , Zhao J , Chen M
Ref : J Insect Sci , 20 : , 2020
Abstract : Plant tannins, polyphenolic plant secondary metabolites are involved in important chemical defense processes in plants. In this study, tannic acid was used as the standard of plant tannins to determine the effects on nutritional indices and activities of glutathione S-transferases (GSTs), cytochrome P450 monooxygenase (CYP450), carboxylesterase (CarE), and acetylcholinesterase (AChE) in fourth-instar larvae of Hyphantria cunea (Drury) by feeding on an artificial diet containing tannic acid under different treatments. We found that tannic acid significantly affected the digestive capacity and food utilization rate of H. cunea larvae. A tannic acid concentration of less than 2.0% promoted feeding and the utilization of undesirable food by H. cunea larvae, while inhibitory effects were observed at high concentrations (>2.5%). Tannic acid had a significant effect on the activity of detoxification enzymes and AChE in H. cunea larvae in concentration-dependent and time-dependent manners (P < 0.05). These results provide new insights into the potential mechanisms underlying detoxification in H. cunea larvae against tannic acid in host plants.
ESTHER : Yuan_2020_J.Insect.Sci_20_
PubMedSearch : Yuan_2020_J.Insect.Sci_20_
PubMedID: 32061083

Title : Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets - Gong_2020_J.Biomed.Nanotechnol_16_827
Author(s) : Gong Y , Lv S , Tian C , Gao Y , Chen B , Wen L , Gao H , Aimaiti W , Ma R , Zhao J , Wang J
Ref : J Biomed Nanotechnol , 16 :827 , 2020
Abstract : Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 mol . L (-1). Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.
ESTHER : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedSearch : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedID: 33187579

Title : Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection - Yang_2020_Mol.Med.Rep__
Author(s) : Yang X , Wei HM , Hu GY , Zhao J , Long LN , Li CJ , Zhao ZJ , Zeng HK , Nie H
Ref : Mol Med Rep , : , 2020
Abstract : Oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. In this study, the antioxidative effects of the antioxidant astaxanthin (AXT) in combination with huperzine A (HupA), which is used as a cholinesterase inhibitor for the treatment of Alzheimer's disease, were investigated. PC12 cells were treated with either tertbutyl hydroperoxide (TBHP), or with the toxic version of betaamyloid, Abeta2535, to induce oxidative stress and neurotoxicity. Cell viability, morphology, lactate dehydrogenase (LDH) release, intracellular accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined, while neuroprotection was also monitored using an MTT assay. It was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by LDH release), attenuated intracellular ROS formation, increased SOD activity and decreased the level of MDA after TBHP exposure when compared to these drugs administered alone. Pretreatment with HupA and AXT decreased toxic damage produced by Abeta2535. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain.
ESTHER : Yang_2020_Mol.Med.Rep__
PubMedSearch : Yang_2020_Mol.Med.Rep__
PubMedID: 31922239

Title : Neuroprotective Effects of D-(-)-Quinic Acid on Aluminum Chloride-Induced Dementia in Rats - Liu_2020_Evid.Based.Complement.Alternat.Med_2020_5602597
Author(s) : Liu L , Liu Y , Zhao J , Xing X , Zhang C , Meng H
Ref : Evid Based Complement Alternat Med , 2020 :5602597 , 2020
Abstract : Objective: The present study was designed to evaluate the neuroprotective effects of D-(-)-quinic acid on aluminum chloride- (AlCl3-) induced neurobehavioral and biochemical changes in rats. This study showed the behavioral and biochemical effects of D-(-)-quinic acid on rats with particular emphasis on the hippocampus and frontal cortex which are associated with memory. Materials and Methods: Chronic administration of aluminum chloride at a dose of 175 mg/kg, p.o. for a period of 25 days markedly increased the level of acetylcholinesterase (AChE) activity and reduced the levels of antioxidant enzymes in the brain. Two doses of D-(-)-quinic acid (200 mg/kg and 400 mg/kg) were selected based on previous safety/toxicity studies and administered orally from the 26th day to the 36th day of the trial. Behavioral parameters were assessed using the Morris water maze test and an actophotometer in rats. Biochemical parameter content and histology of brain tissue were assessed on the final day of the experiment. Results: D-(-)-Quinic acid (200 mg/kg and 400 mg/kg) orally administered alongside AlCl3 rescued AChE activity and the behavioral impairments caused by aluminum. There was significant inhibition of MAO-B in D-(-)-quinic acid-treated rats. Histopathological studies in the hippocampus and cortex of the rat brain also supported that D-(-)-quinic acid markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. These results indicate that D-(-)-quinic acid can reverse memory loss caused by aluminum intoxication by attenuating AChE activity and rescuing the deleterious effect of AlCl3.
ESTHER : Liu_2020_Evid.Based.Complement.Alternat.Med_2020_5602597
PubMedSearch : Liu_2020_Evid.Based.Complement.Alternat.Med_2020_5602597
PubMedID: 32454864

Title : Enantioconvergent hydrolysis of m-nitrostyrene oxide at an elevated concentration by Phaseolus vulgaris epoxide hydrolase in the organic\/aqueous two-phase system - Wen_2020_Lett.Appl.Microbiol_70_181
Author(s) : Wen Z , Zhao J , Liu YY , Zhou JJ , Liu C , Li C , Wu MC
Ref : Lett Appl Microbiol , 70 :181 , 2020
Abstract : (R)-m-Nitrophenyl-1,2-ethanediol (m-NPED) is a versatile and highly value-added chiral building block for the synthesis of some bioactive compounds, such as (R)-Nifenalol. To efficiently produce (R)-m-NPED through the enantioconvergent hydrolysis of racemic (rac-) m-nitrostyrene oxide (m-NSO) using the whole resting cells of Escherichia coli/pCold-pveh2 intracellularly expressing PvEH2, an epoxide hydrolase from Phaseolus vulgaris, two reaction systems were investigated. In the Na2 HPO4 -NaH2 PO4 buffer (50 mmol l(-1) , pH 7.0) system, merely 15 mmol l(-1) rac-m-NSO was successfully subjected to enantioconvergent hydrolysis, producing (R)-m-NPED with 86.0% enantiomeric excess (eep ) and 177.6 mg l(-1) h(-1) space-time yield (STY). The experimental result indicated that there is inhibitory effect of rac-m-NSO at high concentration on PvEH2. To efficiently increase the concentration of rac-m-NSO and the STY of (R)-m-NPED, petroleum ether was first selected to construct an organic/aqueous two-phase system. Then, both the volume ratio (vo /vb ) of petroleum ether to phosphate buffer and the weight ratio (wc /ws ) of E. coli/pCold-pveh2 dry cells to rac-m-NSO were optimized as 2 : 8 and 5 : 1, respectively. In the optimized petroleum ether/phosphate buffer two-phase system, the enantioconvergent hydrolysis of rac-m-NSO at 40 mmol l(-1) (6.6 mg ml(-1) ) was carried out at 25 degrees C for 12 h using 33.0 mg ml(-1) vacuum freeze-dried cells of E. coli/pCold-pveh2, producing (R)-m-NPED with 87.4% eep , 82.3% yield and 502.4 mg l(-1) h(-1) STY. SIGNIFICANCE AND IMPACT OF THE STUDY: Epoxide hydrolases play a crucial role in producing enantiopure epoxides and/or vicinal diols. However, numerous biocatalytic reactions of organic compounds, such as epoxides, in aqueous phase suffered various restrictions. Herein, the enantioconvergent hydrolysis of rac-m-NSO in two reaction systems was investigated using the whole cells of Escherichia coli/pCold-pveh2. As a result, the concentration of rac-m-NSO and the space-time yield of (R)-m-NPED in organic/aqueous two-phase system were significantly increased, when compared with those in aqueous phase. To our knowledge, this is the first report about the production of (R)-m-NPED from rac-m-NSO at an elevated concentration by PvEH2 in the two-phase system.
ESTHER : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedSearch : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedID: 31784998

Title : Genome-Wide Analysis of Serine Carboxypeptidase-Like Acyltransferase Gene Family for Evolution and Characterization of Enzymes Involved in the Biosynthesis of Galloylated Catechins in the Tea Plant (Camellia sinensis) - Ahmad_2020_Front.Plant.Sci_11_848
Author(s) : Ahmad MZ , Li P , She G , Xia E , Benedito VA , Wan XC , Zhao J
Ref : Front Plant Sci , 11 :848 , 2020
Abstract : Tea (Camellia sinensis L.) leaves synthesize and concentrate a vast array of galloylated catechins (e.g., EGCG and ECG) and non-galloylated catechins (e.g., EGC, catechin, and epicatechin), together constituting 8%-24% of the dry leaf mass. Galloylated catechins account for a major portion of soluble catechins in tea leaves (up to 75%) and make a major contribution to the astringency and bitter taste of the green tea, and their pharmacological activity for human health. However, the catechin galloylation mechanism in tea plants is largely unknown at molecular levels. Previous studies indicated that glucosyltransferases and serine carboxypeptidase-like acyltransferases (SCPL) might be involved in the process. However, details about the roles of SCPLs in the biosynthesis of galloylated catechins remain to be elucidated. Here, we performed the genome-wide identification of SCPL genes in the tea plant genome. Several SCPLs were grouped into clade IA, which encompasses previously characterized SCPL-IA enzymes with an acylation function. Twenty-eight tea genes in this clade were differentially expressed in young leaves and vegetative buds. We characterized three SCPL-IA enzymes (CsSCPL11-IA, CsSCPL13-IA, CsSCPL14-IA) with galloylation activity toward epicatechins using recombinant enzymes. Not only the expression levels of these SCPLIA genes coincide with the accumulation of galloylated catechins in tea plants, but their recombinant enzymes also displayed beta-glucogallin:catechin galloyl acyltransferase activity. These findings provide the first insights into the identities of genes encoding glucogallin:catechin galloyl acyltransferases with an active role in the biosynthesis of galloylated catechins in tea plants.
ESTHER : Ahmad_2020_Front.Plant.Sci_11_848
PubMedSearch : Ahmad_2020_Front.Plant.Sci_11_848
PubMedID: 32670320

Title : The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest - Rispe_2020_BMC.Biol_18_90
Author(s) : Rispe C , Legeai F , Nabity PD , Fernandez R , Arora AK , Baa-Puyoulet P , Banfill CR , Bao L , Barbera M , Bouallegue M , Bretaudeau A , Brisson JA , Calevro F , Capy P , Catrice O , Chertemps T , Couture C , Deliere L , Douglas AE , Dufault-Thompson K , Escuer P , Feng H , Forneck A , Gabaldon T , Guigo R , Hilliou F , Hinojosa-Alvarez S , Hsiao YM , Hudaverdian S , Jacquin-Joly E , James EB , Johnston S , Joubard B , Le Goff G , Le Trionnaire G , Librado P , Liu S , Lombaert E , Lu HL , Maibeche M , Makni M , Marcet-Houben M , Martinez-Torres D , Meslin C , Montagne N , Moran NA , Papura D , Parisot N , Rahbe Y , Lopes MR , Ripoll-Cladellas A , Robin S , Roques C , Roux P , Rozas J , Sanchez-Gracia A , Sanchez-Herrero JF , Santesmasses D , Scatoni I , Serre RF , Tang M , Tian W , Umina PA , van Munster M , Vincent-Monegat C , Wemmer J , Wilson ACC , Zhang Y , Zhao C , Zhao J , Zhao S , Zhou X , Delmotte F , Tagu D
Ref : BMC Biol , 18 :90 , 2020
Abstract : BACKGROUND: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. RESULTS: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved > 2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. CONCLUSIONS: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture.
ESTHER : Rispe_2020_BMC.Biol_18_90
PubMedSearch : Rispe_2020_BMC.Biol_18_90
PubMedID: 32698880

Title : Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease - Shen_2020_Front.Pharmacol_11_595254
Author(s) : Shen Y , Zhang B , Pang X , Yang R , Chen M , Zhao J , Wang J , Wang Z , Yu Z , Wang Y , Li L , Liu A , Du G
Ref : Front Pharmacol , 11 :595254 , 2020
Abstract : Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.
ESTHER : Shen_2020_Front.Pharmacol_11_595254
PubMedSearch : Shen_2020_Front.Pharmacol_11_595254
PubMedID: 33390981

Title : Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max - Zhang_2020_Int.J.Biol.Macromol_164_2795
Author(s) : Zhang C , Li C , Zhu XX , Liu YY , Zhao J , Wu MC
Ref : Int J Biol Macromol , 164 :2795 , 2020
Abstract : A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, alpha(S) = 93.7% and beta(R) = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (k(cat)(S)/K(m)(S) = 2.50 mM(-1) s(-1)) of purified GmEH3 for (S)-5a was slightly higher than that (k(cat)(R)/K(m)(R) = 1.52 mM(-1) s(-1)) for (R)-5a, whereas the k(cat)/K(m) (5.16 mM(-1) s(-1)) for (S)-7a was much higher than that (0.09 mM(-1) s(-1)) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 degreesC for 1.5 h afforded (R)-5b with 90.2% ee(p) and 95.4% yield(p), while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ee(s) and 43.2% yield(s). Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
ESTHER : Zhang_2020_Int.J.Biol.Macromol_164_2795
PubMedSearch : Zhang_2020_Int.J.Biol.Macromol_164_2795
PubMedID: 32763395
Gene_locus related to this paper: soybn-GmEH3

Title : Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities - Zhao_2020_J.Ethnopharmacol__113711
Author(s) : Zhao J , Li K , Wang Y , Li D , Wang Q , Xie S , Wang J , Zuo Z
Ref : J Ethnopharmacol , :113711 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.
ESTHER : Zhao_2020_J.Ethnopharmacol__113711
PubMedSearch : Zhao_2020_J.Ethnopharmacol__113711
PubMedID: 33352242

Title : Synthesis, Biological Activity, Molecular Docking Studies of a Novel Series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives as the Acetylcholinesterase Inhibitors - Jin_2020_J.Biomol.Struct.Dyn__1
Author(s) : Jin Z , Zhang C , Liu M , Jiao S , Zhao J , Liu X , Lin H , Wan DC , Hu C
Ref : J Biomol Struct Dyn , :1 , 2020
Abstract : The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer's disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too.
ESTHER : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedSearch : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedID: 32266865

Title : Relief of Cadmium-Induced Intestinal Motility Disorder in Mice by Lactobacillus plantarum CCFM8610 - Liu_2020_Front.Immunol_11_619574
Author(s) : Liu Y , Wu J , Xiao Y , Liu Q , Yu L , Tian F , Zhao J , Zhang H , Chen W , Zhai Q
Ref : Front Immunol , 11 :619574 , 2020
Abstract : Cadmium (Cd) is a toxic metal inducing a range of adverse effects on organs including liver and kidneys. However, the underlying molecular mechanisms of Cd-induced intestinal toxicity through dietary intake is poorly studied. This study evaluated the toxic effects of Cd on intestinal physiology and confirmed the effectiveness of the protective mechanism of the probiotic Lactobacillus plantarum CCFM8610 against chronic Cd toxicity. After treatment with Cd, the HT-29 cell line was subjected to iTRAQ analysis, which revealed that changes in the proteomic profiles after Cd exposure were related to pathways involved in the stress response and carbohydrate metabolism. The results of an animal trial also indicated that 10 weeks of Cd exposure decreased the fecal water content and contractile response of colonic muscle strips in mice, and delayed the excretion time of the first black feces. L. plantarum CCFM8610 treatment provided protective effects against these Cd-induced intestinal motility dysfunctions by recovering the levels of neurotransmitters, including substance P, acetyl cholinesterase, vasoactive intestinal peptide, 5-hydroxytryptamine, calcitonin gene-related peptide, and nitric oxide, and suppressing the cellular stress response in mice (e.g., the inhibition of mitogen-activated protein kinase pathways). The administration of this probiotic was also observed to reduce Cd levels in the tissues and blood of the mice. Our results suggest a newly identified protective mechanism of probiotics against Cd toxicity that involves the recovery of intestinal motility and increase in fecal cadmium excretion.
ESTHER : Liu_2020_Front.Immunol_11_619574
PubMedSearch : Liu_2020_Front.Immunol_11_619574
PubMedID: 33362802

Title : RMS2 encoding a GDSL lipase mediates lipid homeostasis in anthers to determine rice male fertility - Zhao_2020_Plant.Physiol__
Author(s) : Zhao J , Long T , Wang Y , Tong X , Tang J , Li J , Wang H , Tang L , Li Z , Shu Y , Liu X , Li S , Liu H , Wu Y , Zhang J
Ref : Plant Physiol , : , 2020
Abstract : Plant male gametogenesis is a coordinated effort involving both reproductive tissues and sporophytic tissues, in which lipid metabolism plays an essential role. Although GDSL esterases/lipases have been well known as key enzymes for many plant developmental processes and stress responses, their functions in reproductive development remain unclear. Here, we report the identification of a rice male sterile 2 (rms2) mutant in rice (Oryza sativa), which is completely male sterile due to the defects in tapetum degradation, cuticle formation in sporophytic tissues, and impaired exine and central vacuole development in pollen grains. RMS2 was map-based cloned as an endoplasmic reticulum-localized GDSL lipase gene, which is predominantly transcribed during early anther development. In rms2, a three-nucleotides deletion and one base substitution (TTGT to A) occurred within the GDSL domain, which reduced the lipid hydrolase activity of the resulting protein and led to significant changes in the content of 16 lipid components and numerous other metabolites as revealed by a comparative metabolic analysis. Furthermore, RMS2 is directly targeted by male fertility regulators Undeveloped Tapetum 1 (UDT1) and Persistent Tapetal Cell 1 (PTC1) both in vitro and in vivo, suggesting that RMS2 may serve as a key node in the rice male fertility regulatory network. These findings shed light on the function of GDSLs in reproductive development and provide a promising gene resource for hybrid rice breeding.
ESTHER : Zhao_2020_Plant.Physiol__
PubMedSearch : Zhao_2020_Plant.Physiol__
PubMedID: 32029522

Title : Instrument-free and visual detection of organophosphorus pesticide using a smartphone by coupling aggregation-induced emission nanoparticle and two-dimension MnO(2) nanoflake - Chen_2020_Biosens.Bioelectron_170_112668
Author(s) : Chen J , Chen X , Zhao J , Liu S , Chi Z
Ref : Biosensors & Bioelectronics , 170 :112668 , 2020
Abstract : Given the importance of food safety, it is highly desirable to develop a convenient, low-cost, and practical sensor for organophosphorus pesticides (OPs) detection. Here, a fluorescent paper analytical device (FPAD) based on aggregation-induced emission (AIE) nanoparticles (PTDNPs-0.10) and two-dimension MnO(2) nanoflakes (2D-MnNFs) was developed for instrument-free and naked-eye analysis of OPs. PTDNP-MnNFs composites were obtained through 2D-MnNFs and PTDNPs-0.10 by electrostatic interaction and the fluorescence emission of PTDNPs-0.10 was quenched through fluorescence resonance energy transfer (FRET). When acetylcholinesterase (AChE) was present, acetylthiocholine (ATCh) was catalytically hydrolyzed into thiocholine, which reduced MnO(2) of PTDNP-MnNFs into Mn(2+), subsequently blocking the FRET and enhancing the fluorescence. Upon the addition of OP, AChE activity was depressed and thus the FRET between 2D-MnNFs and PTDNPs-0.10 was not affected, resulting in a slight change in fluorescence. On the basis of the variation in fluorescence intensity, highly sensitive detection of OP was readily achieved with a detection limit of 0.027 ng/mL; on the basis of the variation in brightness of FPAD, instrument-free and visual detection of OP was realized using a smartphone with a detection limit of 0.73 ng/mL. The application of FPAD has significantly simplified the detection procedure and decreased the test cost, supplying a new approach for on-site detection of OPs.
ESTHER : Chen_2020_Biosens.Bioelectron_170_112668
PubMedSearch : Chen_2020_Biosens.Bioelectron_170_112668
PubMedID: 33032200

Title : Donepezil prevents ox-LDL-induced attachment of THP-1 monocytes to human aortic endothelial cells (HAECs) - Zhou_2020_Chem.Res.Toxicol__
Author(s) : Zhou S , Li Z , Liu P , Wang S , Zhao J , Zhang G
Ref : Chemical Research in Toxicology , : , 2020
Abstract : Oxidized low-density lipoprotein (ox-LDL)- induced endothelial insults plays an important role in the pathogenesis of atherosclerosis. Donepezil is a well-known acetylcholinesterase inhibitor, with its primary application being the treatment of Alzheimer's disease. More recently, there has been increased interest in donepezil as an anti-atherosclerosis treatment as it possesses a host of relevant and potentially beneficial properties. In the present study, we found that donepezil could reduce the expression of lectin-type oxidized low-density lipoprotein receptor-1 (LOX-1)in human aortic endothelial cells (HAECs). We found that donepezil could suppress the expression of intercellular adhesion molecule-1 (ICAM-1), which recruits monocytes to adhere to the endothelium, by more than half. Another key finding of our study is that donepezil could reduce the expression of tumor necrosis factor receptor-alpha (TNF-alpha) and interleukin-6 (IL-6) by more than half at both the mRNA and protein transcriptional levels. Donepezil also reduced the expression of tissue factor (TF), which is considerably upregulated in atherosclerotic lesions, by more than half. Finally, we turned our attention to the early growth response protein-1 (Egr-1) for its potential role in mediating the effects of donepezil. Through our Egr-1 overexpression experiment, we found that overexpression of Egr-1 almost completely abolished the effects of donepezil described above. Thus, the effects of donepezil are likely mediated through downregulation of Egr-1. These findings provide evidence that donepezil may exert protective effects against atherosclerosis.
ESTHER : Zhou_2020_Chem.Res.Toxicol__
PubMedSearch : Zhou_2020_Chem.Res.Toxicol__
PubMedID: 32174113

Title : Significant improvement in catalytic activity and enantioselectivity of a Phaseolus vulgaris epoxide hydrolase, PvEH3, towards ortho-cresyl glycidyl ether based on the semi-rational design - Zhang_2020_Sci.Rep_10_1680
Author(s) : Zhang C , Liu Y , Li C , Xu Y , Su Y , Li J , Zhao J , Wu M
Ref : Sci Rep , 10 :1680 , 2020
Abstract : The investigation of substrate spectrum towards five racemic (rac-) aryl glycidyl ethers (1a-5a) indicated that E. coli/pveh3, an E. coli BL21(DE3) transformant harboring a PvEH3-encoding gene pveh3, showed the highest EH activity and enantiomeric ratio (E) towards rac-3a. For efficiently catalyzing the kinetic resolution of rac-3a, the activity and E value of PvEH3 were further improved by site-directed mutagenesis of selected residues. Based on the semi-rational design of an NC-loop in PvEH3, four single-site variants of pveh3 were amplified by PCR, and intracellularly expressed in E. coli BL21(DE3), respectively. E. coli/pveh3(E134K) and /pveh3(T137P) had the enhanced EH activities of 15.3 +/- 0.4 and 16.1 +/- 0.5 U/g wet cell as well as E values of 21.7 +/- 1.0 and 21.2 +/- 1.1 towards rac-3a. Subsequently, E. coli/pveh3(E134K/T137P) harboring a double-site variant gene was also constructed, having the highest EH activity of 22.4 +/- 0.6 U/g wet cell and E value of 24.1 +/- 1.2. The specific activity of the purified PvEH3(E134K/T137P) (14.5 +/- 0.5 U/mg protein) towards rac-3a and its catalytic efficiency (k(cat)/K(m) of 5.67 mM(-1) s(-1)) for (S)-3a were 1.7- and 3.54-fold those (8.4 +/- 0.3 U/mg and 1.60 mM(-1) s(-1)) of PvEH3. The gram-scale kinetic resolution of rac-3a using whole wet cells of E. coli/pveh3(E134K/T137P) was performed at 20 degC for 7.0 h, producing (R)-3a with 99.4% ee(s) and 38.5 +/- 1.2% yield. Additionally, the mechanism of PvEH3(E134K/T137P) with remarkably improved E value was analyzed by molecular docking simulation.
ESTHER : Zhang_2020_Sci.Rep_10_1680
PubMedSearch : Zhang_2020_Sci.Rep_10_1680
PubMedID: 32015448
Gene_locus related to this paper: phavu-PvEH3

Title : DL0410 attenuates oxidative stress and neuroinflammation via BDNF\/TrkB\/ERK\/CREB and Nrf2\/HO-1 activation - Zhang_2020_Int.Immunopharmacol_86_106729
Author(s) : Zhang B , Zhao J , Wang Z , Xu L , Liu A , Du G
Ref : Int Immunopharmacol , 86 :106729 , 2020
Abstract : Oxidative stress and neuroinflammation have been deeply associated with Alzheimer's disease. DL0410 is a novel acetylcholinesterase inhibitor with potential anti-oxidative effects in AD-related animal models, while the specific mechanism has not been fully clarified. In this study, DL0410 was predicted to be related to the modification of cell apoptosis, oxidation-reduction process, inflammatory response and ERK1/ERK2 cascade by in silico target fishing and GO enrichment analysis. Then the possible protective effects of DL0410 were evaluated by hydrogen peroxide (H2O2)-induced oxidative stress model and lipopolysaccharides (LPS)-induced neuroinflammation model H2O2 decreased the viability of SH-SY5Y cells, induced malondialdehyde (MDA) accumulation, mitochondrial membrane potential (Deltapsim) loss and cell apoptosis, which could be reversed by DL0410 dose-dependently, indicating that DL0410 protected SH-SY5Y cells against H2O2-mediated oxidative stress. Western blot analysis showed that DL0410 increased the H2O2-triggered down-regulated TrkB, ERK and CREB phosphorylation and the expression of BDNF. In addition, TrkB inhibitor ANA-12, ERK inhibitor SCH772984 and CREB inhibitor 666-15 eliminated the inhibition of DL0410 on MDA accumulation and Deltapsim loss. Furthermore, DL0410 attenuates inflammatory responses and ROS production in LPS-treated BV2 cells, which is responsible for Nrf2 and HO-1 up-regulation. The present study demonstrates that DL0410 is a potential activator of the BDNF/TrkB/ERK/CREB and Nrf2/HO-1 pathway and may be a potential candidate for regulating oxidative stress and neuroinflammatory response in the brain. Together, the results showed that DL0410 is a promising drug candidate for treating AD and possibly other nervous system diseases associated with oxidative stress and neuroinflammation.
ESTHER : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedSearch : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedID: 32645628

Title : Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6\/JAK2\/STAT3 signaling in glioma - Zhou_2020_Cell.Oncol.(Dordr)_43_461
Author(s) : Zhou J , Jiang Y , Zhao J , Zhang H , Fu J , Luo P , Ma Y , Zou D , Gao H , Hu J , Zhang Y , Jing Z
Ref : Cell Oncol (Dordr) , 43 :461 , 2020
Abstract : PURPOSE: The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown. METHODS: Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays. RESULTS: We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling. CONCLUSIONS: Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
ESTHER : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedSearch : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedID: 32207044
Gene_locus related to this paper: human-NDRG2

Title : Structural and functional analyses of the lipase CinB from Enterobacter asburiae - Shang_2019_Biochem.Biophys.Res.Commun_519_274
Author(s) : Shang F , Lan J , Liu W , Chen Y , Wang L , Zhao J , Chen J , Gao P , Ha NC , Quan C , Nam KH , Xu Y
Ref : Biochemical & Biophysical Research Communications , 519 :274 , 2019
Abstract : Lipases are widely present in various plants, animals and microorganisms, constituting a large category of enzymes. They have the ability to catalyze the cleavage of ester bonds. The lipase CinB from Enterobacter asburiae (E. asburiae) is an acetyl esterase. The primary amino acid sequence suggests that the EaCinB protein belongs to the alpha/beta-hydrolase (ABH) superfamily of the esterase/lipase superfamily. However, its molecular functions have not yet been determined. Here, we report the crystal structure of E. asburiae CinB at a 1.45A resolution. EaCinB contains a signal peptide, cap domain and catalytic domain. The active site of EaCinB contains the catalytic triad (Ser180-His307-Asp277) on the catalytic domain. The oxyanion hole is composed of Gly106 and Gly107 within the conserved sequence motif HGGG (amino acid residues 106-109). The substrate is accessible between the alpha1 and alpha2 helices or the alpha1 helix and catalytic domain. Narrow substrate pockets are formed by the alpha2 helix of the cap domain. Site-directed mutagenesis showed that EaCinB-W208H exhibits a higher catalytic ability than EaCinB-WT by approximately nine times. Our results provide insight into the molecular function of EaCinB.
ESTHER : Shang_2019_Biochem.Biophys.Res.Commun_519_274
PubMedSearch : Shang_2019_Biochem.Biophys.Res.Commun_519_274
PubMedID: 31493870
Gene_locus related to this paper: entas-cinB

Title : Use of high-throughput enzyme-based assay with xenobiotic metabolic capability to evaluate the inhibition of acetylcholinesterase activity by organophosphorous pesticides - Li_2019_Toxicol.In.Vitro_56_93
Author(s) : Li S , Zhao J , Huang R , Santillo MF , Houck KA , Xia M
Ref : Toxicol In Vitro , 56 :93 , 2019
Abstract : The inhibition of acetylcholinesterase (AChE) has pharmaceutical applications as well as potential neurotoxic effects. The in vivo metabolites of some chemicals including organophosphorus pesticides can become more potent AChE inhibitors compared to their parental compounds. To account for the effects of biotransformation, we have developed and characterized a high-throughput screening method for identifying AChE inhibitors that become active or more potent following xenobiotic metabolism. In this study, an enzyme-based assay was developed in 1536-well plates using recombinant human AChE combined with human or rat liver microsomes. The AChE activity was measured by two methods with different readouts: colorimetric and fluorescent. The assay exhibited exceptional performance characteristics including large assay signal window, low well-to-well variability and high reproducibility. The performance of the assays with microsomes was characterized by testing a group of known AChE inhibitors including parent compounds and their metabolites. Large potency differences between the parent compounds and the metabolites were observed in the assay with microsome addition. Both assay readouts were required for maximal sensitivity. These results demonstrate that this platform is a promising method to profile large numbers of chemicals that require metabolic activation for inhibiting AChE activity.
ESTHER : Li_2019_Toxicol.In.Vitro_56_93
PubMedSearch : Li_2019_Toxicol.In.Vitro_56_93
PubMedID: 30625376

Title : Enhanced Diffusion and Oligomeric Enzyme Dissociation - Jee_2019_J.Am.Chem.Soc_141_20062
Author(s) : Jee AY , Chen K , Tlusty T , Zhao J , Granick S
Ref : Journal of the American Chemical Society , 141 :20062 , 2019
Abstract : The concept that catalytic enzymes can act as molecular machines transducing chemical activity into motion has conceptual and experimental support, but experimental support has involved oligomeric enzymes, often studied under conditions where the substrate concentration is higher than biologically relevant and accordingly exceeds kM, the Michaelis constant. Urease, a hexamer of subunits, has been considered to be the gold standard demonstrating enhanced diffusion. Here we show that urease and certain other oligomeric enzymes dissociate above kM into their subunits that diffuse more rapidly, thus providing a simple physical mechanism that contributes to enhanced diffusion in this regime of concentrations. Mindful that this conclusion may be controversial, our findings are supported by four independent analytical techniques: static light scattering, dynamic light scattering (DLS), size-exclusion chromatography (SEC), and fluorescence correlation spectroscopy (FCS). Data for urease are emphasized and the conclusion is validated for hexokinase, acetylcholinesterase, and aldolase. For hexokinase and aldolase no enhanced diffusion is observed except under conditions when these oligomeric enzymes dissociate. At substrate concentration regimes below kM at which acetylcholinesterase and urease do not dissociate, our finding showing up to 10% enhancement of the diffusion coefficient is consistent with various theoretical scenarios in the literature.
ESTHER : Jee_2019_J.Am.Chem.Soc_141_20062
PubMedSearch : Jee_2019_J.Am.Chem.Soc_141_20062
PubMedID: 31778607

Title : Reduced systemic exposure and brain uptake of donepezil in rats with scopolamine-induced cognitive impairment - Zhao_2019_Xenobiotica__1
Author(s) : Zhao J , Ren T , Yang M , Zhang Y , Wang Q , Zuo Z
Ref : Xenobiotica , :1 , 2019
Abstract : 1. Donepezil (DPZ) is an acetylcholinesterase (AchE) inhibitor used in the mild to moderately severe Alzheimer's disease. Among its major metabolites, 6-O-desmethyl DPZ (6-DDPZ), 5-O-desmethyl DPZ (5-DDPZ) and DPZ N-oxide, the anti-AchE activities of 5-DDPZ and DPZ N-oxide have never been clearly identified before. Besides, there is no report on simultaneous determination of DPZ and its three metabolites in the brain, thus their uptake in hippocampus and cortex are unknown. Therefore, the current studies are proposed aiming to 1) investigate the anti-AchE activities and brain uptake of DPZ and its three metabolites and 2) compare their pharmacokinetics and brain uptake between normal and scopolamine-induced rats. 2. DPZ and its three metabolites demonstrated anti-AchE activities with the IC50 in the order of DPZ (7.20 x 10(-2) muM), 6-DDPZ (1.14 x 10(-1) muM), 5-DDPZ (4.03 x 10(-1) muM) and DPZ N-oxide (1.61 muM). They were also evenly distributed in the brain and retained much longer in the brain than that in plasma in normal rats. 3. Comparing to normal rats, Cmax, AUC0-->24h and AUC0-->infinity of DPZ were reduced by 52.0%, 31.2% and 30.1%, respectively; Tmax of DPZ and its three metabolites were prolonged and their brain uptake were decreased in scopolamine-induced rats, suggesting the potential reduced absorption of DPZ.
ESTHER : Zhao_2019_Xenobiotica__1
PubMedSearch : Zhao_2019_Xenobiotica__1
PubMedID: 31298070

Title : Seawater acidification increases copper toxicity: A multi-biomarker approach with a key marine invertebrate, the Pacific Oyster Crassostrea gigas - Cao_2019_Aquat.Toxicol_210_167
Author(s) : Cao R , Zhang T , Li X , Zhao Y , Wang Q , Yang D , Qu Y , Liu H , Dong Z , Zhao J
Ref : Aquat Toxicol , 210 :167 , 2019
Abstract : Ocean acidification (OA) has been found to increase the release of free Cu(2+) in seawater. However, only a handful of studies have investigated the influence of OA on Cu accumulation and cellular toxicity in bivalve species. In this study, Pacific oysters, Crassostrea gigas, were exposed to 25 mug/L Cu(2+) at three pH levels (8.1, 7.8 and 7.6) for 14 and 28 days. Physiological and histopathological parameters [(clearance rate (CR), respiration rate (RR), histopathological damage and condition index (CI)), oxidative stress and neurotoxicity biomarkers [superoxide dismutase (SOD) and glutathione transferase (GST) activities, lipid peroxidation (LPO) and acetylcholinesterase (AChE) activity], combined with glycolytic enzyme activities [pyruvate kinase (PK) and hexokinase (HK)] were investigated in C. gigas. The bioconcentration of Cu was increased in soft tissues of Cu-exposed oysters under OA. Our results suggest that both OA and Cu could lead to physiological disturbance, oxidative stress, cellular damage, disturbance in energy metabolism and neurotoxicity in oysters. The inhibited CR, increased glycolytic enzymes activities and decreased CI suggested that the energy metabolism strategy adopted by oysters was not sustainable in the long term. Furthermore, integrated biomarker response (IBR) results found that OA and Cu exposure lead to severe stress to oysters, and co-exposure was the most stressful condition. Results from this study highlight the need to include OA in future environmental assessments of pollutants and hazardous materials to better elucidate the risks of those environmental perturbations.
ESTHER : Cao_2019_Aquat.Toxicol_210_167
PubMedSearch : Cao_2019_Aquat.Toxicol_210_167
PubMedID: 30870663

Title : Molecular and functional properties of two Spodoptera exigua acetylcholinesterase genes - Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
Author(s) : Zhao J , Hao D , Xiao L , Tan Y , Jiang Y , Bai L , Wang K
Ref : Archives of Insect Biochemistry & Physiology , :e21554 , 2019
Abstract : Acetylcholinesterase (AChE) is a vital enzyme that hydrolyzes acetylcholine. Here, full-length complementary DNAs (cDNAs) of two acetylcholinesterase genes (SeAce1 and SeAce2) were obtained from Spodoptera exigua, a widespread phytophagous pest in agriculture. The complete SeAce1 cDNA comprised 5447 nucleotides including an open reading frame (ORF) encoding 694 amino acids, while SeAce2 cDNA encompassed a 1917-bp ORF which would likely yield 638 amino acids. Both SeAce1 and SeAce2 contained specific characteristics of functional AChE. A phylogenetic tree of all lepidopteran insect Aces showed S. exigua clustered with S. litura, Helicoverpa assulta, and H. armigera, all of which are Noctuidae. In S. exigua, SeAce1 gene expression levels (reverse transcription polymerase chain reaction [RT-PCR] and quantitative RT-PCR) were markedly increased compared with SeAce2 in all developmental phases and tissue types. Both genes were down regulated by inserting the corresponding dsRNAs in 5th instar larvae, which resulted in 56.7% (SeAce1) and 24.6% (SeAce2) death. Downregulation of both SeAce1 and SeAce2 significantly reduced fecundity and vitellogenin gene expression in S. exigua. These results revealed the biological functions of the two Ace genes (SeAce1 and SeAce2), providing novel insights into the development of strategies for controlling insect pests.
ESTHER : Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
PubMedSearch : Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
PubMedID: 31033012
Gene_locus related to this paper: spolt-ACHE2 , spolt-ACHE1

Title : Candida sp. 99-125 lipase-catalyzed synthesis of ergosterol linolenate and its characterization - He_2019_Food.Chem_280_286
Author(s) : He WS , Li L , Zhao J , Xu H , Rui J , Cui D , Li H , Zhang H , Liu X
Ref : Food Chem , 280 :286 , 2019
Abstract : As a major sterol in edible mushroom, ergosterol has gained much attention owing to its potential bioactivities. However, ergosterol has a high melting point, poor oil solubility and stability, which restrict its scope of application. In this study, an ergosterol ester of alpha-linolenic acid was successfully and efficiently prepared using Candida sp. 99-125 lipase as a biocatalyst. The desired product was confirmed to be ergosterol linolenate using MS, FT-IR, and NMR analyses. Using Candida sp. 99-125 lipase, the product conversion exceeded 92% in 12h under the following optimized parameters: 75mmol/L ergosterol, 40g/L lipase, 1:1.25 ergosterol-to-alpha-linolenic acid molar ratio, and 45 degrees C. The results confirmed that Candida sp. 99-125 lipase has good reusability and stability and is also relatively low cost, suggesting its great potential for large-scale production of ergosterol ester. Most importantly, the physiochemical properties (oil solubility and melting point) of ergosterol significantly improved after esterification with alpha-linolenic acid, thus facilitating its application in oil-based systems.
ESTHER : He_2019_Food.Chem_280_286
PubMedSearch : He_2019_Food.Chem_280_286
PubMedID: 30642499

Title : Hydrolytic Metabolism of Cyanopyrrolidine DPP-4 Inhibitors Mediated by Dipeptidyl Peptidases - Kong_2019_Drug.Metab.Dispos_47_238
Author(s) : Kong F , Pang X , Zhao J , Deng P , Zheng M , Zhong D , Chen X
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 47 :238 , 2019
Abstract : Nitrile group biotransformation is an unusual or minor metabolic pathway for most nitrile-containing drugs. However, for some cyanopyrrolidine dipeptidyl peptidase 4 (DPP-4) inhibitors (vildagliptin, anagliptin, and besigliptin, but not saxagliptin), the conversion of nitrile group into carboxylic acid is their major metabolic pathway in vivo. DPP-4 was reported to be partly involved in the metabolism. In our pilot study, it was also observed that saxagliptin, a DPP-4 specific inhibitor, decreased the plasma exposures of besigliptin carboxylic acid in rats by only 20%. Therefore, it is speculated that some other enzymes may participate in nitrile group hydrolysis. After incubating gliptins with the cytosol, microsomes, and mitochondria of liver and kidney, carboxylic acid metabolites could all be formed. In recombinant DPP family such as DPP-4, DPP-2, DPP-8, DPP-9, and fibroblast activation protein-alpha, more hydrolytic metabolites were found. Among them, DPP-2 had the highest hydrolytic capacity besides DPP-4, and the DPP-4 inhibitor saxagliptin and DPP-2 inhibitor AX8819 can both inhibit the hydrolysis of gliptins. Western blot results showed that DPP-2 and DPP-4 existed in the aforementioned subcellular organelles at varying amounts. In rats, AX8819 decreased the plasma exposures of besigliptin carboxylic acid by 40%. The amide intermediates of gliptins were detected in vivo and in vitro. When the amide derivatives of gliptins were incubated with DPP-4, they were completely hydrolyzed at a rate far more than that from the parent drug, including saxagliptin-amide. Therefore, it was proposed that gliptins, except saxagliptin, were initially hydrolyzed to their amides by DPPs, which was the rate-limiting step in generating the carboxylic end product.
ESTHER : Kong_2019_Drug.Metab.Dispos_47_238
PubMedSearch : Kong_2019_Drug.Metab.Dispos_47_238
PubMedID: 30530814

Title : Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease - Sun_2019_J.Cell.Mol.Med_23_887
Author(s) : Sun Z , Chang B , Huang A , Hao S , Gao M , Sun Y , Shi M , Jin L , Zhang W , Zhao J , Teng G , Han L , Tian H , Liang Q , Zhang JY , Zou Z
Ref : J Cell Mol Med , 23 :887 , 2019
Abstract : Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin-33 (IL-33) is a newly identified member of the IL-1 cytokine family and is released as an "alarmin" during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL-33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end-stage liver disease and Child-Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil-associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide-activated monocytes down-regulated transmembrane ST2 receptor but up-regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor-alpha (TNF-alpha). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF-alpha production. In addition, although plasma IL-33 levels were comparable between healthy controls and ALD patients, we found the IL-33 expression in liver tissues from ALD patients was down-regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL-33-positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL-33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.
ESTHER : Sun_2019_J.Cell.Mol.Med_23_887
PubMedSearch : Sun_2019_J.Cell.Mol.Med_23_887
PubMedID: 30478965

Title : A sensitive fluorescence assay of organophosphorus pesticides using acetylcholinesterase and copper-catalyzed click chemistry - Huang_2019_Analyst_144_3436
Author(s) : Huang N , Qin Y , Li M , Chen T , Lu M , Zhao J
Ref : Analyst , 144 :3436 , 2019
Abstract : Organophosphorus pesticides (OPs) are widely used in agricultural fields, but exhibit high toxicity to human beings. A sensitive fluorescence assay for organophosphorus pesticides was developed using the inhibition of acetylcholinesterase (AChE) activity and the copper-catalyzed click chemical reaction. In the click reaction, two hybridized DNA probes can be ligated with copper ions, inducing a fluorescence quenching during the strand displacement reaction. AChE can hydrolyze acetylthiocholine (ATCh) to form thiocholine (TCh) which contains a thiol group. TCh will react with copper ions, blocking the click reaction and a high fluorescence signal is observed. But in the presence of OPs, the activity of AChE is inhibited, releasing a high concentration of copper ions that catalyze the click chemical reaction and resulting in decreased fluorescence signals. Taking advantage of the copper-mediated signal amplification effect, the sensitivity was improved. This assay has also been applied to detect OPs in river water samples with satisfactory results, which demonstrates that the method has great potential for practical applications in environmental protection and food safety fields.
ESTHER : Huang_2019_Analyst_144_3436
PubMedSearch : Huang_2019_Analyst_144_3436
PubMedID: 31020297

Title : Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection - Jia_2019_Emerg.Microbes.Infect_8_760
Author(s) : Jia W , Channappanavar R , Zhang C , Li M , Zhou H , Zhang S , Zhou P , Xu J , Shan S , Shi X , Wang X , Zhao J , Zhou D , Perlman S , Zhang L
Ref : Emerg Microbes Infect , 8 :760 , 2019
Abstract : The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naive hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
ESTHER : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedSearch : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedID: 31130102

Title : Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease - Hu_2019_Brain.Pathol_29_502
Author(s) : Hu YT , Chen XL , Huang SH , Zhu QB , Yu SY , Shen Y , Sluiter A , Verhaagen J , Zhao J , Swaab D , Bao AM
Ref : Brain Pathology , 29 :502 , 2019
Abstract : Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild-type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD.
ESTHER : Hu_2019_Brain.Pathol_29_502
PubMedSearch : Hu_2019_Brain.Pathol_29_502
PubMedID: 30511454

Title : Bioactive Compounds Isolated from Marine Bacterium Vibrio neocaledonicus and Their Enzyme Inhibitory Activities - Gomez-Betancur_2019_Mar.Drugs_17_
Author(s) : Gomez-Betancur I , Zhao J , Tan L , Chen C , Yu G , Rey-Suarez P , Preciado L
Ref : Mar Drugs , 17 : , 2019
Abstract : Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 +/- 1.1 muM), to AChE, and XO (51.3% and 44.3% at 50 mug/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 +/- 0.39 muM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 mug/mL) and weak activity to AChE (25.7% at 50 mug/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 mug of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites.
ESTHER : Gomez-Betancur_2019_Mar.Drugs_17_
PubMedSearch : Gomez-Betancur_2019_Mar.Drugs_17_
PubMedID: 31288374

Title : Multiple site-directed mutagenesis of a Phaseolus vulgaris epoxide hydrolase to improve its catalytic performance towards p-chlorostyrene oxide based on the computer-aided re-design - Li_2019_Int.J.Biol.Macromol_121_326
Author(s) : Li C , Zhao J , Hu D , Hu BC , Wang R , Zang J , Wu MC
Ref : Int J Biol Macromol , 121 :326 , 2019
Abstract : To improve the activity and regioselectivity of a Phaseolus vulgaris epoxide hydrolase (PvEH3) towards p-chlorostyrene oxide (pCSO), the site-directed mutagenesis was conducted based on the computer-aided re-design. Firstly, seven single-site variants of a PvEH3-encoding gene (pveh3) were constructed as designed theoretically and expressed in E. coli BL21(DE3), respectively. One transformant, E. coli/pveh3(G170E), had the higher EH activity towards racemic pCSO, while both E. coli/pveh3(F187L) and /pveh3(P237L) with enhanced regioselectivity coefficient alphaS values. Secondly, to combine their respective merits, the double- and triple-site variants, pveh3(G170E/F187L), pveh3(G170E/P237L) and pveh3(G170E/F187L/P237L), were also constructed. Among all E. coli transformants, E. coli/pveh3(G170E/F187L/P237L) simultaneously had the highest EH activity of 20.3U/g wet cell and alphaS value of 95.2%, by which the hydrolysis of rac-pCSO enantioconvergently produced (R)-p-chlorophenylethane-1,2-diol with an enantiomeric excess of 93.2%. Furthermore, PvEH3(G170E/F187L/P237L) expressed in E. coli/pveh3(G170E/F187L/P237L) was purified. Its specific activity and catalytic efficiency towards rac-pCSO were 4.1U/mg protein and 1.81mM(-1)s(-1), which were 3.0- and 3.1-fold those of PvEH3. Finally, the molecular docking simulation analysis indicated that PvEH3(G170E/F187L/P237L) preferentially attacks the more hindered benzylic carbon of (S)-pCSO over PvEH3, which was consistent with their alphaS values measured experimentally.
ESTHER : Li_2019_Int.J.Biol.Macromol_121_326
PubMedSearch : Li_2019_Int.J.Biol.Macromol_121_326
PubMedID: 30308283
Gene_locus related to this paper: phavu-PvEH3

Title : Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation - Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
Author(s) : Gan L , Guo M , Si J , Zhang J , Liu Z , Zhao J , Wang F , Yan J , Li H , Zhang H
Ref : Artif Cells Nanomed Biotechnol , 47 :4202 , 2019
Abstract : Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 muM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.
ESTHER : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedSearch : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedID: 31713449

Title : A low trans margarine fat analog to beef tallow for healthier formulations: Optimization of enzymatic interesterification using soybean oil and fully hydrogenated palm oil - Li_2018_Food.Chem_255_405
Author(s) : Li Y , Zhao J , Xie X , Zhang Z , Zhang N , Wang Y
Ref : Food Chem , 255 :405 , 2018
Abstract : The health hazard of tallow and partial hydrogenated oils is well known in margarine productions. For this, food manufactures are urged to develop novel alternatives for healthier margarine formulations. The highest interesterification degree acquired with lipase Lipozyme 435 standing out from other catalysts (solid acid, sodium hydroxide and methoxide) was applied to produce low trans margarine fat analogs to beef tallow (BT) with the blend of soybean oil (SO) and fully hydrogenated palm oil (FHPO) in a mass ratio of 4:3. Reaction parameters like enzyme dosage (4.2 wt%), temperature (95 degreeC) and time (245 min) were optimized using the Box-Behnken design. Regarding fatty acid profiles, triacylglycerol species, solid fat content, polymorphism, melting and crystallization behaviors, the resulting interesterified oil was characterized in comparison with BT, FHPO and the SO-FHPO blend so as to prove its potential in formulating low trans fat margarines because of desirable physicochemical properties and polymorphs.
ESTHER : Li_2018_Food.Chem_255_405
PubMedSearch : Li_2018_Food.Chem_255_405
PubMedID: 29571493

Title : Effects of acute and chronic exposures of fluoxetine on the Chinese fish, topmouth gudgeon Pseudorasbora parva - Chen_2018_Ecotoxicol.Environ.Saf_160_104
Author(s) : Chen H , Zeng X , Mu L , Hou L , Yang B , Zhao J , Schlenk D , Dong W , Xie L , Zhang Q
Ref : Ecotoxicology & Environmental Safety , 160 :104 , 2018
Abstract : Fluoxetine is a selective serotonin reuptake inhibitor used as an antidepressant and has been frequently detected in aquatic environments. However, its effects in fish from Asia remain relatively less studied. In this study, the topmouth gudgeon Pseudorasbora parva was exposed to 0, 50, and 200microg/L of fluoxetine for 4h and 42 d. The effects of fluoxetine on biometrics were compared to biochemical endpoints indicative of stress in different fish tissues (brain, liver, gills and intestine) following exposures. In fish exposed for 42 d, lipid peroxidation endpoints were enhanced 80% in the liver and gills. Acetylcholinesterase (AChE) activity was increased 40% after exposure to 50microg/L and 55% at 200microg/L following 4h exposure. In contrast AChE was increased 26% (at 50microg/L) after 42 d of exposures. Enhanced ethoxyresorufin-O-deethylase activity (EROD) was detected only in fish exposed to 50microg/L of fluoxetine for 4h. The activity of alpha-glucosidase (alpha-Glu) was also induced (at 200microg/L) after 4h of exposure. After 4h of exposure, the activities of proteases in the intestine were generally inhibited at 200microg/L. Both 4h and 42 d exposures resulted in an increased hepatosomatic index (HSI) but did not affect the condition factor (CF). Our results demonstrate that fluoxetine significantly altered biochemical endpoints in P. parva after acute exposure and the morphological changes in liver size were not observed until 42d of exposure.
ESTHER : Chen_2018_Ecotoxicol.Environ.Saf_160_104
PubMedSearch : Chen_2018_Ecotoxicol.Environ.Saf_160_104
PubMedID: 29793199

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Post-Injury Administration of Galantamine Reduces Traumatic Brain Injury Pathology and Improves Outcome - Zhao_2018_J.Neurotrauma_35_362
Author(s) : Zhao J , Hylin MJ , Kobori N , Hood KN , Moore AN , Dash PK
Ref : Journal of Neurotrauma , 35 :362 , 2018
Abstract : Acetylcholine is an excitatory neurotransmitter in the central nervous system that plays a key role in cognitive function, including learning and memory. Previous studies have shown that experimental traumatic brain injury (TBI) reduces cholinergic neurotransmission, decreases evoked release of acetylcholine, and alters cholinergic receptor levels. Galantamine (U.S. Food and Drug Administration approved for the treatment of vascular dementia and Alzheimer's disease) has been shown to inhibit acetylcholinesterase activity and allosterically potentiate nicotinic receptor signaling. We investigated whether acute administration of galantamine can reduce TBI pathology and improve cognitive function tested days after the termination of the drug treatment. Post-injury administration of galantamine was found to decrease TBI-triggered blood-brain barrier (BBB) permeability (tested 24 h post-injury), attenuate the loss of both GABAergic and newborn neurons in the ipsilateral hippocampus, and improve hippocampal function (tested 10 days after termination of the drug treatment). Specifically, significant improvements in the Morris water maze, novel object recognition, and context-specific fear memory tasks were observed in injured animals treated with galantamine. Although messenger RNAs for both M1 (Nos2, TLR4, and IL-12ss) and M2 (Arg1, CCL17, and Mcr1) microglial phenotypes were elevated post-TBI, galantamine treatment did not alter microglial polarization tested 24 h and 6 days post-injury. Taken together, these findings support the further investigation of galantamine as a treatment for TBI.
ESTHER : Zhao_2018_J.Neurotrauma_35_362
PubMedSearch : Zhao_2018_J.Neurotrauma_35_362
PubMedID: 29088998

Title : Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma - Yao_2017_Medicine.(Baltimore)_96_e6735
Author(s) : Yao Q , Bao X , Xue R , Liu H , Li J , Dong J , Duan Z , Ren M , Zhao J , Song Q , Yu H , Zhu Y , Lu J , Meng Q
Ref : Medicine (Baltimore) , 96 :e6735 , 2017
Abstract : This study aimed to determine if the immunoscore (IS) staging system would be a potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO), respectively. ImagePro Plus software was used in the calculation of the paraffin-embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV-HCC tissue demonstrated that there were higher density and larger area of lymphocytes in the invasive margins (IM) region than in the center (CT). Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma-glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P = .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis showed that TNM staging was not an independent prognostic factor of DFS and OS. Our results showed ISs did not have a significantly correlation with DFS (P = .35, .19, and .07, respectively), but it was correlated significantly with OS (P = .00, .00, and .00, respectively). There were statistical differences among the OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS staging was closely related to the outcome of patients. It can compensate the TNM tumor classification system in predicting the prognosis of HBV-HCC patients.
ESTHER : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedSearch : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedID: 28445292

Title : Silencing of juvenile hormone epoxide hydrolase gene (Nljheh) enhances short wing formation in a macropterous strain of the brown planthopper, Nilaparvata lugens - Zhao_2017_J.Insect.Physiol_102_18
Author(s) : Zhao J , Zhou Y , Li X , Cai W , Hua H
Ref : J Insect Physiol , 102 :18 , 2017
Abstract : The rice brown planthopper, Nilaparvata lugens, is an important migratory pest in many rice planting areas of Asia. The typical wing dimorphism of N. lugens gives them flexibility to adapt to different environmental cues. As an important hormone in the insect's endocrine regulation, juvenile hormone (JH) has previously been shown to participate in the wing morph determination of N. lugens. In this paper, we investigated the possible wing morph determination roles of two JH metabolic enzymes, JH esterase (JHE) and JH epoxide hydrolase (JHEH). A 1957-bp full-length cDNA sequence encoding JHEH in N. lugens (NlJHEH) was first cloned from a hemipteran insect. Except for an uncertain transmembrane segment prediction, the deduced 454-amino-acid sequence of Nljheh has all of the conserved domains of JHEHs such as the H(147)GWP(150), Tyr293 and Tyr368 motif corresponding to the oxyanion hole and the residues Asp222, Glu398, and His425 in the catalytic triad. qRT-PCR results showed that both Nljhe and Nljheh had different expression timeframes between a predominantly brachypterous strain (BS) and a macropterous strain (MS) of N. lugens, indicating that these two enzymes may participate in wing dimorphism regulation in brown planthopper. Silencing Nljheh expression by dsRNA injection enhanced short wing formation in the macropterous strain of N. lugens, while the brachypterizing individuals were mainly females. Compared to the dsgfp injection control, silencing Nljhe had no brachypterizing effect. Our results indicated that NlJHEH plays an important role in the wing morph determination of N. lugens.
ESTHER : Zhao_2017_J.Insect.Physiol_102_18
PubMedSearch : Zhao_2017_J.Insect.Physiol_102_18
PubMedID: 28867330

Title : Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells - Yang_2017_Mol.Neurobiol_54_788
Author(s) : Yang H , Liu C , Chen B , An J , Zhang R , Zhang Q , Zhao J , He B , Hao DJ
Ref : Molecular Neurobiology , 54 :788 , 2017
Abstract : Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings.
ESTHER : Yang_2017_Mol.Neurobiol_54_788
PubMedSearch : Yang_2017_Mol.Neurobiol_54_788
PubMedID: 27566610

Title : Hypermethylation of the N-Myc Downstream-Regulated Gene 2 Promoter in Peripheral Blood Mononuclear Cells is Associated with Liver Fibrosis in Chronic Hepatitis B - Liu_2017_Tohoku.J.Exp.Med_241_155
Author(s) : Liu XY , Fan YC , Gao S , Zhao J , Li F , Zhang J , Wang K
Ref : Tohoku J Exp Med , 241 :155 , 2017
Abstract : DNA methylation is a fundamental epigenetic modification to regulate gene expression. N-Myc downstream-regulated gene (NDRG) 2 is a cytoplasmic protein and participates in the pathogenesis of liver fibrosis. In this study, the mRNA expression and methylation status of NDRG2 was evaluated in patients with chronic hepatitis B (CHB). The study included 143 CHB patients and 65 normal controls (NC). The mRNA expression of NDRG2 in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction. The methylation status of the NDRG2 promoter in PBMCs was detected by methylation-specific polymerase chain reaction. The NDRG2 mRNA level was lower in the CHB group than in the NC group (p < 0.001). Methylation frequency of the NDRG2 promoter was significantly higher in CHB patients than in the NC group (52.44% vs. 26.15%, p < 0.001). Importantly, the relative expression levels of NDRG2 mRNA were significantly lower in the methylated group than in the unmethylated group in both CHB patients and NC (p < 0.001). Furthermore, a lower mRNA level and hypermethylation of NDRG2 were associated with liver fibrosis and inflammation grade in CHB. The aspartate aminotransferase-to-platelet ratio index (APRI) score is widely used to predict liver fibrosis. The mRNA expression levels and methylation status of NDRG2 showed a better score compared to APRI for discriminating the severity of liver fibrosis. In conclusion, hypermethylation of NDRG2 in PBMCs was correlated with decreased mRNA expression and with liver fibrosis. The methylation status of the NDRG2 promoter in PBMCs is a potential noninvasive biomarker to predict the severity of liver fibrosis.
ESTHER : Liu_2017_Tohoku.J.Exp.Med_241_155
PubMedSearch : Liu_2017_Tohoku.J.Exp.Med_241_155
PubMedID: 28202850

Title : Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients - Zhao_2017_Oncotarget_8_33864
Author(s) : Zhao J , Li Z , Cong Y , Zhang J , Tan M , Zhang H , Geng N , Li M , Yu W , Shan P
Ref : Oncotarget , 8 :33864 , 2017
Abstract : Repetitive transcranial magnetic stimulation (rTMS) acts as a kind of widely-applied and non-invasive method in the intervention of some neurological disorders. This prospective, randomized, double-blind, placebo-controlled trial investigates the effect of rTMS on 30 cases of Alzheimer's disease (AD) participants, who were classified into mild and moderate groups. Neuropsychological tests were carried out using the AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) before, immediately after, and 6 weeks after the intervention. In this work, data from 30 AD patients revealed that there was no obvious interaction effect of time-by-group. The ADAS-cog, MMSE and WHO-UCLA AVLT score in the rTMS group was significantly improved compared with baselines at 6 weeks after treatment (all p<0.05). Meanwhile, MoCA scores were also obviously ameliorated in the mild AD patients with rTMS. Besides, subgroup analysis showed that the effect of rTMS on the memory and language of mild AD patients was superior to those of moderate AD patients. In conclusion, our findings suggested that repetitive transcranial magnetic stimulation improves cognitive function, memory and language level of AD patients, especially in the mild stage of AD. Thus, rTMS can be recommended as a promising adjuvant therapy combined with cholinesterase inhibitors at the mild stage of AD patients.
ESTHER : Zhao_2017_Oncotarget_8_33864
PubMedSearch : Zhao_2017_Oncotarget_8_33864
PubMedID: 27823981

Title : Ultra-Fast Degradation of Chemical Warfare Agents Using MOF-Nanofiber Kebabs - Zhao_2016_Angew.Chem.Int.Ed.Engl_55_13224
Author(s) : Zhao J , Lee DT , Yaga RW , Hall MG , Barton HF , Woodward IR , Oldham CJ , Walls HJ , Peterson GW , Parsons GN
Ref : Angew Chem Int Ed Engl , 55 :13224 , 2016
Abstract : The threat associated with chemical warfare agents (CWAs) motivates the development of new materials to provide enhanced protection with a reduced burden. Metal-organic frame-works (MOFs) have recently been shown as highly effective catalysts for detoxifying CWAs, but challenges still remain for integrating MOFs into functional filter media and/or protective garments. Herein, we report a series of MOF-nanofiber kebab structures for fast degradation of CWAs. We found TiO2 coatings deposited via atomic layer deposition (ALD) onto polyamide-6 nanofibers enable the formation of conformal Zr-based MOF thin films including UiO-66, UiO-66-NH2 , and UiO-67. Cross-sectional TEM images show that these MOF crystals nucleate and grow directly on and around the nanofibers, with strong attachment to the substrates. These MOF-functionalized nanofibers exhibit excellent reactivity for detoxifying CWAs. The half-lives of a CWA simulant compound and nerve agent soman (GD) are as short as 7.3 min and 2.3 min, respectively. These results therefore provide the earliest report of MOF-nanofiber textile composites capable of ultra-fast degradation of CWAs.
ESTHER : Zhao_2016_Angew.Chem.Int.Ed.Engl_55_13224
PubMedSearch : Zhao_2016_Angew.Chem.Int.Ed.Engl_55_13224
PubMedID: 27653957

Title : Novel nonquaternary reactivators showing reactivation efficiency for soman-inhibited human acetylcholinesterase - Wei_2016_Toxicol.Lett_246_1
Author(s) : Wei Z , Liu YQ , Wang YA , Li WH , Zhou XB , Zhao J , Huang CQ , Li XZ , Liu J , Zheng ZB , Li S
Ref : Toxicol Lett , 246 :1 , 2016
Abstract : Soman is a highly toxic nerve agent with strong inhibition of acetylcholinesterase (AChE), but of the few reactivators showing antidotal efficiency for soman-inhibited AChE presently are all permanently charged cationic oximes with poor penetration of the blood-brain barrier. To overcome this problem, uncharged reactivators have been designed and synthesized, but few of them were efficient for treating soman poisoning. Herein, we used a dual site biding strategy to develop more efficient uncharged reactivators. The ortho-hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. The in vitro experiment demonstrated that some of the resulting conjugates have robust activity against soman-inhibited AChE, and oxime 8b was highlighted as the most efficient one. Although not good as HI-6 in vitro, these new compounds hold promise for development of more efficient centrally acting reactivators for soman poisoning due to their novel nonquaternary structures, which are predicted to be able to cross the blood-brain barrier.
ESTHER : Wei_2016_Toxicol.Lett_246_1
PubMedSearch : Wei_2016_Toxicol.Lett_246_1
PubMedID: 26809136

Title : Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel - Qiu_2016_Front.Pharmacol_7_366
Author(s) : Qiu ZX , Gao WC , Dai Y , Zhou SF , Zhao J , Lu Y , Chen XJ , Li N
Ref : Front Pharmacol , 7 :366 , 2016
Abstract : Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 microg h/L, p < 0.05) and CAM (10119 vs. 2634 microg h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L h(-1) kg(-1), p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL h(-1) kg(-1)) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver.
ESTHER : Qiu_2016_Front.Pharmacol_7_366
PubMedSearch : Qiu_2016_Front.Pharmacol_7_366
PubMedID: 27774067

Title : Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4 - Li_2016_J.Infect.Dis_213_712
Author(s) : Li K , Wohlford-Lenane C , Perlman S , Zhao J , Jewell AK , Reznikov LR , Gibson-Corley KN , Meyerholz DK , McCray PB, Jr.
Ref : J Infect Dis , 213 :712 , 2016
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV-infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.
ESTHER : Li_2016_J.Infect.Dis_213_712
PubMedSearch : Li_2016_J.Infect.Dis_213_712
PubMedID: 26486634

Title : Serum vitamin D3 does not correlate with liver fibrosis in chronic hepatitis C - Ren_2015_World.J.Gastroenterol_21_11152
Author(s) : Ren Y , Liu M , Zhao J , Ren F , Chen Y , Li JF , Zhang JY , Qu F , Zhang JL , Duan ZP , Zheng SJ
Ref : World J Gastroenterol , 21 :11152 , 2015
Abstract : AIM: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC).
METHODS: From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, gamma-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry.
RESULTS: Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades. CONCLUSION: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.
ESTHER : Ren_2015_World.J.Gastroenterol_21_11152
PubMedSearch : Ren_2015_World.J.Gastroenterol_21_11152
PubMedID: 26494969

Title : The Synergistic Effects of Heat Shock Protein 70 and Ginsenoside Rg1 against Tert-Butyl Hydroperoxide Damage Model In Vitro - Lu_2015_Oxid.Med.Cell.Longev_2015_437127
Author(s) : Lu D , Xu A , Mai H , Zhao J , Zhang C , Qi R , Wang H , Zhu L
Ref : Oxid Med Cell Longev , 2015 :437127 , 2015
Abstract : Neural stem cells (NSCs) transplanted is one of the hottest research to treat Alzheimer's disease (AD), but cholinergic neurons from stem cells were also susceptible to cell death which Heat shock protein 70 (HSP70) was affirmed to reverse. Related to cognitive impairment, cholinergic nervous cells should be investigated and ginsenoside Rg1 (G-Rg1) was considered to increase them. We chose tert-butyl hydroperoxide (t-BHP) damage model to study in vitro. Functional properties of our recombination plasmid pEGFP-C2-HSP70 were affirmed by SH-SY5Y cells. To opposite the transitory appearance of HSP70, NSCs used as the vectors of HSP70 gene overexpressed HSP70 for at least 7 days in vitro. After transfection for 3 days, G-Rg1 pretreatment for 4 hours, and coculture for 3 days, the expression of acetylcholinesterase (ChAT), synaptophysin, and the ratio of NeuN and GFAP were assessed by western blot; Morphological properties were detected by 3D reconstruction and immunofluorescence. ChAT was markedly improved in the groups contained G-Rg1. In coculture system, the ratio of neurons/astrocytes and the filaments of neurons were increased; apoptosis cells were decreased, compared to monotherapy (P < 0.05). In conclusion, we demonstrated that, as a safe cotreatment affirmed in vitro, overexpression of HSP70 in NSCs plus G-Rg1 promoted nervous cells regeneration from chronic oxidative damage.
ESTHER : Lu_2015_Oxid.Med.Cell.Longev_2015_437127
PubMedSearch : Lu_2015_Oxid.Med.Cell.Longev_2015_437127
PubMedID: 25685255

Title : Biodegradation and Mineralization of Polystyrene by Plastic-Eating Mealworms: Part 1. Chemical and Physical Characterization and Isotopic Tests - Yang_2015_Environ.Sci.Technol_49_12080
Author(s) : Yang Y , Yang J , Wu WM , Zhao J , Song Y , Gao L , Yang R , Jiang L
Ref : Environ Sci Technol , 49 :12080 , 2015
Abstract : Polystyrene (PS) is generally considered to be durable and resistant to biodegradation. Mealworms (the larvae of Tenebrio molitor Linnaeus) from different sources chew and eat Styrofoam, a common PS product. The Styrofoam was efficiently degraded in the larval gut within a retention time of less than 24 h. Fed with Styrofoam as the sole diet, the larvae lived as well as those fed with a normal diet (bran) over a period of 1 month. The analysis of fecula egested from Styrofoam-feeding larvae, using gel permeation chromatography (GPC), solid-state (13)C cross-polarization/magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy, and thermogravimetric Fourier transform infrared (TG-FTIR) spectroscopy, substantiated that cleavage/depolymerization of long-chain PS molecules and the formation of depolymerized metabolites occurred in the larval gut. Within a 16 day test period, 47.7% of the ingested Styrofoam carbon was converted into CO2 and the residue (ca. 49.2%) was egested as fecula with a limited fraction incorporated into biomass (ca. 0.5%). Tests with alpha (13)C- or beta (13)C-labeled PS confirmed that the (13)C-labeled PS was mineralized to (13)CO2 and incorporated into lipids. The discovery of the rapid biodegradation of PS in the larval gut reveals a new fate for plastic waste in the environment.
ESTHER : Yang_2015_Environ.Sci.Technol_49_12080
PubMedSearch : Yang_2015_Environ.Sci.Technol_49_12080
PubMedID: 26390034

Title : Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication - Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
Author(s) : Yang K , Tian Z , Chen C , Luo L , Zhao B , Wang Z , Yu L , Li Y , Sun Y , Li W , Chen Y , Zhang Y , Ai D , Zhao J , Shang C , Ma Y , Wu B , Wang M , Gao L , Sun D , Zhang P , Guo F , Wang W , Wang J , Varshney RK , Ling HQ , Wan P
Ref : Proc Natl Acad Sci U S A , 112 :13213 , 2015
Abstract : Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean.
ESTHER : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedSearch : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedID: 26460024
Gene_locus related to this paper: phaan-a0a0l9ttq5 , phaan-a0a0l9vh69 , phaan-a0a0l9vh89 , phaan-a0a0s3tc53 , vigrr-a0a1s3v914 , phaan-a0a0s3s998 , phaan-a0a0s3siv8 , phaan-a0a0l9uys5 , phaan-a0a0s3rp07 , phaan-a0a0s3rbq0 , vigrr-a0a1s3tul4 , phaan-a0a0s3smk7 , phaan-a0a0s3slm9 , phaan-a0a0l9ujf5 , phaan-a0a0l9til9 , phaan-a0a0l9uqr2 , phaan-a0a0l9v1m8 , phaan-a0a0l9uc60 , phaan-a0a0l9ucr8

Title : Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia - Xu_2015_Mar.Drugs_13_3653
Author(s) : Xu L , Dong W , Zhao J , Xu Y
Ref : Mar Drugs , 13 :3653 , 2015
Abstract : Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs), isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA). PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0) till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE) activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression.
ESTHER : Xu_2015_Mar.Drugs_13_3653
PubMedSearch : Xu_2015_Mar.Drugs_13_3653
PubMedID: 26058015

Title : Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients - Xu_2014_Mol.Biol.Rep_41_4133
Author(s) : Xu X , Xiong Z , Zhang L , Liu Y , Lu L , Peng Y , Guo H , Zhao J , Xia K , Hu Z
Ref : Mol Biol Rep , 41 :4133 , 2014
Abstract : Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were "Probably Damaging". The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case-control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95% CI 2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population.
ESTHER : Xu_2014_Mol.Biol.Rep_41_4133
PubMedSearch : Xu_2014_Mol.Biol.Rep_41_4133
PubMedID: 24570023

Title : Evidence of polyethylene biodegradation by bacterial strains from the guts of plastic-eating waxworms - Yang_2014_Environ.Sci.Technol_48_13776
Author(s) : Yang J , Yang Y , Wu WM , Zhao J , Jiang L
Ref : Environ Sci Technol , 48 :13776 , 2014
Abstract : Polyethylene (PE) has been considered nonbiodegradable for decades. Although the biodegradation of PE by bacterial cultures has been occasionally described, valid evidence of PE biodegradation has remained limited in the literature. We found that waxworms, or Indian mealmoths (the larvae of Plodia interpunctella), were capable of chewing and eating PE films. Two bacterial strains capable of degrading PE were isolated from this worm's gut, Enterobacter asburiae YT1 and Bacillus sp. YP1. Over a 28-day incubation period of the two strains on PE films, viable biofilms formed, and the PE films' hydrophobicity decreased. Obvious damage, including pits and cavities (0.3-0.4 mum in depth), was observed on the surfaces of the PE films using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The formation of carbonyl groups was verified using X-ray photoelectron spectroscopy (XPS) and microattenuated total reflectance/Fourier transform infrared (micro-ATR/FTIR) imaging microscope. Suspension cultures of YT1 and YP1 (10(8) cells/mL) were able to degrade approximately 6.1 +/- 0.3% and 10.7 +/- 0.2% of the PE films (100 mg), respectively, over a 60-day incubation period. The molecular weights of the residual PE films were lower, and the release of 12 water-soluble daughter products was also detected. The results demonstrated the presence of PE-degrading bacteria in the guts of waxworms and provided promising evidence for the biodegradation of PE in the environment.
ESTHER : Yang_2014_Environ.Sci.Technol_48_13776
PubMedSearch : Yang_2014_Environ.Sci.Technol_48_13776
PubMedID: 25384056

Title : Rapid generation of a mouse model for Middle East respiratory syndrome - Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
Author(s) : Zhao J , Li K , Wohlford-Lenane C , Agnihothram SS , Fett C , Gale MJ, Jr. , Baric RS , Enjuanes L , Gallagher T , McCray PB, Jr. , Perlman S
Ref : Proc Natl Acad Sci U S A , 111 :4970 , 2014
Abstract : In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.
ESTHER : Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
PubMedSearch : Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970
PubMedID: 24599590

Title : DWARF3 participates in an SCF complex and associates with DWARF14 to suppress rice shoot branching - Zhao_2014_Plant.Cell.Physiol_55_1096
Author(s) : Zhao J , Wang T , Wang M , Liu Y , Yuan S , Gao Y , Yin L , Sun W , Peng L , Zhang W , Wan J , Li X
Ref : Plant Cell Physiol , 55 :1096 , 2014
Abstract : Strigolactones (SLs) are a novel class of plant hormones that inhibit shoot branching. Currently, two proteins in rice are thought to play crucial roles in SL signal transduction. DWARF14 (D14), an alpha/beta hydrolase, is responsible for SL perception, while DWARF3 (D3), an F-box protein with leucine-rich repeats, is essential for SL signal transduction. However, how these two proteins transmit SL signals to downstream factors remains unclear. Here, we characterized a high-tillering dwarf rice mutant, gsor300097, which is insensitive to GR24, a synthetic analog of SL. Mapping and sequencing analysis showed that gsor300097 is a novel allelic mutant of D3, in which a nonsense mutation truncates the protein from 720 to 527 amino acids. The D3 gene was strongly expressed in root, leaf, shoot base and panicle. Nuclear-localized F-box protein D3 played a role in the SCF complex by interacting with OSK1, OSK5 or OSK20 and OsCullin1. In addition, D3 associated with D14 in a GR24-dependent manner in vivo. Taken together, our findings suggested that D3 assembled into an SCF(D3) complex and associated with D14 to suppress rice shoot branching.
ESTHER : Zhao_2014_Plant.Cell.Physiol_55_1096
PubMedSearch : Zhao_2014_Plant.Cell.Physiol_55_1096
PubMedID: 24616269

Title : Heterologous overexpression of Vigna radiata epoxide hydrolase in Escherichia coli and its catalytic performance in enantioconvergent hydrolysis of p-nitrostyrene oxide into (R)-p-nitrophenyl glycol - Zhu_2014_Appl.Microbiol.Biotechnol_98_207
Author(s) : Zhu QQ , He WH , Kong XD , Fan LQ , Zhao J , Li SX , Xu JH
Ref : Applied Microbiology & Biotechnology , 98 :207 , 2014
Abstract : Two native epoxide hydrolases (EHs) were previously discovered from mung bean powder (Vigna radiata), both of which can catalyze the enantioconvergent hydrolysis of p-nitrostyrene oxide (pNSO). In this study, the encoding gene of VrEH1 was successfully cloned from the cDNA of V. radiata by RT-PCR and rapid amplification of cDNA ends (RACE) technologies. High homologies were found to two putative EHs originated from Glycine max (80%) and Medicago truncatula (79%). The vreh1 gene constructed in pET28a(+) vector was then heterologously overexpressed in Escherichia coli BL21(DE3), and the encoded protein was purified to homogeneity by nickel affinity chromatography. It was shown that VrEH1 has an optimum activity at 45 degrees C and is very thermostable with an inactivation energy of 468 kJ mol(-1). The enzyme has no apparent requirement of metal ions for activity, and its activity was strongly inhibited by 1 mM of Ni(2+), Cu(2+), Fe(2+), or Co(2+). By adding 0.1% Triton X-100, the enzyme activity could be significantly increased up to 340%. VrEH1 shows an unusual ability of enantioconvergent catalysis for the hydrolysis of racemic pNSO, affording (R)-p-nitrophenyl glycol (pNPG). It displays opposite regioselectivity toward (S)-pNSO (83% to Calpha) in contrast to (R)-pNSO (87% to Cbeta). The K M and k cat of VrEH1 were determined to be 1.4 mM and 0.42 s(-1) for (R)-pNSO and 5.5 mM and 6.2 s(-1) for (S)-pNSO. This thermostable recombinant VrEH1 with enantioconvergency is considered to be a promising biocatalyst for the highly productive preparation of enantiopure vicinal diols and also a good model for understanding the mechanism of EH stereoselectivity.
ESTHER : Zhu_2014_Appl.Microbiol.Biotechnol_98_207
PubMedSearch : Zhu_2014_Appl.Microbiol.Biotechnol_98_207
PubMedID: 23615737
Gene_locus related to this paper: vigra-e5l4l1

Title : Fe(3)O(4) magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent - Liang_2013_Anal.Chem_85_308
Author(s) : Liang M , Fan K , Pan Y , Jiang H , Wang F , Yang D , Lu D , Feng J , Zhao J , Yang L , Yan X
Ref : Analytical Chemistry , 85 :308 , 2013
Abstract : Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 muM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.
ESTHER : Liang_2013_Anal.Chem_85_308
PubMedSearch : Liang_2013_Anal.Chem_85_308
PubMedID: 23153113

Title : Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73T - Lin_2013_Genome.Announc_1_e00972
Author(s) : Lin Z , Liu Z , Yang R , Zou Y , Wan D , Chen J , Guo M , Zhao J , Fang C , Liu F
Ref : Genome Announc , 1 : , 2013
Abstract : Lactobacillus shenzhenensis strain LY-73(T) is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of Lactobacillus shenzhenensis LY-73(T).
ESTHER : Lin_2013_Genome.Announc_1_e00972
PubMedSearch : Lin_2013_Genome.Announc_1_e00972
PubMedID: 24265500
Gene_locus related to this paper: 9laco-u4tvs6 , 9laco-u4ti93

Title : A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides - Yi_2013_Anal.Chem_85_11464
Author(s) : Yi Y , Zhu G , Liu C , Huang Y , Zhang Y , Li H , Zhao J , Yao S
Ref : Analytical Chemistry , 85 :11464 , 2013
Abstract : Sensitive, rapid, and simple detection methods for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents are in urgent demand. A novel label-free silicon quantum dots (SiQDs)-based sensor was designed for ultrasensitive detection of pesticides. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce betaine and H2O2 which can quench the photoluminescence (PL) of SiQDs. Upon the addition of pesticides, the activity of AChE is inhibited, leading to the decrease of the generated H2O2, and hence the PL of SiQDs increases. By measuring the increase in SiQDs PL, the inhibition efficiency of pesticide to AChE activity was evaluated. It was found that the inhibition efficiency was linearly dependent on the logarithm of the pesticides concentration. Consequently, pesticides, such as carbaryl, parathion, diazinon, and phorate, were determined with the SiQDs PL sensing method. The lowest detectable concentrations for carbaryl, parathion, diazinon, and phorate reached 7.25 x 10(-9), 3.25 x 10(-8), 6.76 x 10(-8), and 1.9 x 10(-7) g/L, respectively, which were much lower than those previously reported. The detecting results of pesticide residues in food samples via this method agree well with those from high-performance liquid chromatography. The simple strategy reported here should be suitable for on-site pesticides detection, especially in combination with other portable platforms.
ESTHER : Yi_2013_Anal.Chem_85_11464
PubMedSearch : Yi_2013_Anal.Chem_85_11464
PubMedID: 24160846

Title : Whole-Genome Sequence of Microcystis aeruginosa TAIHU98, a Nontoxic Bloom-Forming Strain Isolated from Taihu Lake, China - Yang_2013_Genome.Announc_1_e00333
Author(s) : Yang C , Zhang W , Ren M , Song L , Li T , Zhao J
Ref : Genome Announc , 1 : , 2013
Abstract : Microcystis aeruginosa is a dominant bloom-forming cyanobacterium in many freshwater lakes. This report describes the first whole-genome sequence of the nontoxic strain of M. aeruginosa TAIHU98, which was isolated from Taihu Lake in eastern China.
ESTHER : Yang_2013_Genome.Announc_1_e00333
PubMedSearch : Yang_2013_Genome.Announc_1_e00333
PubMedID: 23766403

Title : Effects of dietary isoleucine on growth, the digestion and absorption capacity and gene expression in hepatopancreas and intestine of juvenile Jian carp (Cyprinus carpio var. Jian) - Zhao_2012_Aquaculture_368-369_117
Author(s) : Zhao J , Liu Y , Jiang J , Wu P , Chen G , Jiang W , Li S , Tang L , Kuang S , Feng L , Zhou X
Ref : Aquaculture , 368-369 :117 , 2012
Abstract : The present research studied the effects of dietary isoleucine (Ile) on growth performance, the digestion and absorption capacity, as well as gene expression in hepatopancreas and intestine of juvenile Jian carp (Cyprinus carpio var. Jian). A total of 1200 juvenile Jian carp (Cyprinus carpio var. Jian) (6.90.03g) were randomly distributed into six groups with four replicates each, fed semi-purified isonitrogenous diets (335.8g crude protein/kg diet) containing graded levels of Ile (4.2, 7.0, 9.5, 11.9, 13.9 and 16.9g/kg diets) for 60days. The relative expression of gene was performed by real-time quantitative PCR. Compared with the control group, Ile supplementation increased (P<0.05): (1) specific growth rate (SGR) and feed intake, (2) body protein content and protein retention value, (3) intestine fold height, (4) activities of trypsin, chymotrypsin, lipase and amylase in hepatopancreas and intestine, (5) activities of alkaline phosphatase in distal intestine, Na+/K+-ATPase and -glutamyl transpeptidase in intestine, (6) glutamateoxaloacetate transaminase activity in hepatopancreas, and (7) relative mRNA expression of chymotrypsin, lipase and amylase in hepatopancreas, -glutamyl transpeptidase in mid intestine, Na+/K+-ATPase in intestine and target of rapamycin (TOR) in hepatopancreas and mid intestine. However, Ile supplementation decreased (P<0.05): (1) feed conversion ratio, (2) glutamatepyruvate transaminase activity in hepatopancreas, and (3) relative mRNA expression of trypsin in hepatopancreas, alkaline phosphatase in intestine, -glutamyl transpeptidase in distal intestine and eIF4E-binding protein (4E-BP) in hepatopancreas, proximal and mid intestine. Collectively, this study indicated that dietary Ile improves fish growth, promotes the digestive and absorptive ability and regulates gene expression of the digestive and brush border enzymes, TOR and 4E-BP. Based on the quadratic regression analysis of SGR, the Ile requirement of juvenile Jian carp (6.9063.39g) was estimated to be a 12.9g/kg diet, corresponding to 38.4g/kg of dietary protein.
ESTHER : Zhao_2012_Aquaculture_368-369_117
PubMedSearch : Zhao_2012_Aquaculture_368-369_117
PubMedID:
Gene_locus related to this paper: cypca-s4s6y9

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

Title : Quantitative structure-activity relationship of organophosphate compounds based on molecular interaction fields descriptors - Zhao_2012_Environ.Toxicol.Pharmacol_35_228
Author(s) : Zhao J , Yu S
Ref : Environ Toxicol Pharmacol , 35 :228 , 2012
Abstract : By using multi-block partial least-squares (MBPLS) method, quantitative structure-activity relationship (QSAR) between 35 organophosphate compounds (OP) and their 24h acute toxicities towards the housefly (Musca nebulo L.) was built on the molecular interaction fields (MIF) descriptors, which were obtained with O, N and DRY as probes, and then normalised with block unscaled weights (BUW) technique. The best QSAR model had 8 principal components, with the coefficient of determination R(2)=0.995 and that of leave-one-out cross-validation Q(2)=0.865, and the corresponding standard deviation of error 0.076 and 0.361, respectively. Block importance in the prediction (BIP) for O, N and DRY probe were 1.030, 0.962 and 1.007, respectively. Contour map of variable coefficients showed that hydrogen bonding between the O atom in PO and the NH groups in acetylcholinesterase (AChE) played an important role in the interaction between OP and AChE. Meanwhile, the hydrophobicity of OP also had significant contribution. QSAR based on the MIF descriptors could be a potential means to interpret the mechanisms of ligand-receptor interaction when the receptor was well known.
ESTHER : Zhao_2012_Environ.Toxicol.Pharmacol_35_228
PubMedSearch : Zhao_2012_Environ.Toxicol.Pharmacol_35_228
PubMedID: 23348103

Title : Comparison of four prognostic models and a new Logistic regression model to predict short-term prognosis of acute-on-chronic hepatitis B liver failure - He_2012_Chin.Med.J.(Engl)_125_2272
Author(s) : He WP , Hu JH , Zhao J , Tong JJ , Ding JB , Lin F , Wang HF
Ref : Chinese Medical Journal (Engl) , 125 :2272 , 2012
Abstract : BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically severe disease associated with major life-threatening complications including hepatic encephalopathy and hepatorenal syndrome. The aim of this study was to evaluate the short-term prognostic predictability of the model for end-stage liver disease (MELD), MELD-based indices, and their dynamic changes in patients with ACLF-HBV, and to establish a new model for predicting the prognosis of ACLF-HBV. METHODS: A total of 172 patients with ACLF-HBV who stayed in the hospital for more than 2 weeks were retrospectively recruited. The predictive accuracy of MELD, MELD-based indices, and their dynamic change (D) were compared using the area under the receiver operating characteristic curve method. The associations between mortality and patient characteristics were studied by univariate and multivariate analyses. RESULTS: The 3-month mortality was 43.6%. The largest concordance (c) statistic predicting 3-month mortality was the MELD score at the end of 2 weeks of admission (0.8), followed by the MELD: sodium ratio (MESO) (0.796) and integrated MELD (iMELD) (0.758) scores, DMELD (0.752), DMESO (0.729), and MELD plus sodium (MELD-Na) (0.728) scores. In multivariate Logistic regression analysis, the independent factors predicting prognosis were hepatic encephalopathy (OR = 3.466), serum creatinine, international normalized ratio (INR), and total bilirubin at the end of 2 weeks of admission (OR = 10.302, 6.063, 5.208, respectively), and cholinesterase on admission (OR = 0.255). This regression model had a greater prognostic value (c = 0.85, 95%CI 0.791 - 0.909) compared to the MELD score at the end of 2 weeks of admission (Z = 4.9851, P = 0.0256). CONCLUSIONS: MELD score at the end of 2 weeks of admission is a useful predictor for 3-month mortality in ACLF-HBV patients. Hepatic encephalopathy, serum creatinine, international normalized ratio, and total bilirubin at the end of 2 weeks of admission and cholinesterase on admission are independent predictors of 3-month mortality.
ESTHER : He_2012_Chin.Med.J.(Engl)_125_2272
PubMedSearch : He_2012_Chin.Med.J.(Engl)_125_2272
PubMedID: 22882847

Title : Repeated exposures to chlorpyrifos lead to spatial memory retrieval impairment and motor activity alteration - Yan_2012_Neurotoxicol.Teratol_34_442
Author(s) : Yan C , Jiao L , Zhao J , Yang H , Peng S
Ref : Neurotoxicology & Teratology , 34 :442 , 2012
Abstract : Chlorpyrifos (CPF) is one of the most commonly used insecticides throughout the world and has become one of the major pesticides detected in farm products. Chronic exposures to CPF, especially at the dosages without eliciting any systemic toxicity, require greater attention. The purpose of this study was, therefore, to evaluate the behavioral effects of repeated low doses (doses that do not produce overt signs of cholinergic toxicity) of CPF in adult rats. Male rats were given 0, 1.0, 5.0 or 10.0mg/kg of CPF through intragastric administration daily for 4 consecutive weeks. The behavioral functions were assessed in a series of behavioral tests, including water maze task, open-field test, grip strength and rotarod test. Furthermore, the present study was designed to evaluate the effects of repeated exposures to CPF on water maze recall and not acquisition. The results showed that the selected doses only had mild inhibition effects on cholinesterase activity, and have no effects on weight gain and daily food consumption. Performances in the spatial retention task (Morris water maze) were impaired after the 4-week exposure to CPF, but the performances of grip strength and rotarod test were not affected. Motor activities in the open field were changed, especially the time spent in the central zone increased. The results indicated that repeated exposures to low doses of CPF may lead to spatial recall impairments, behavioral abnormalities. However, the underlying mechanism needs further investigations.
ESTHER : Yan_2012_Neurotoxicol.Teratol_34_442
PubMedSearch : Yan_2012_Neurotoxicol.Teratol_34_442
PubMedID: 22640976

Title : Genome sequence of Streptomyces auratus strain AGR0001, a phoslactomycin-producing actinomycete - Han_2012_J.Bacteriol_194_5472
Author(s) : Han X , Li M , Ding Z , Zhao J , Ji K , Wen M , Lu T
Ref : Journal of Bacteriology , 194 :5472 , 2012
Abstract : Streptomyces auratus strain AGR0001 produces neophoslactomycin A, a novel analog of phoslactomycin that possesses potent activity against some phytopathogenic fungi. Here, the draft genome sequence of S. auratus strain AGR0001 is presented, which would provide insight into the biosynthetic mechanism of neophoslactomycin A.
ESTHER : Han_2012_J.Bacteriol_194_5472
PubMedSearch : Han_2012_J.Bacteriol_194_5472
PubMedID: 22965094
Gene_locus related to this paper: 9acto-j2ju40 , 9acto-j1zwn4 , 9acto-j2a066 , 9acto-j2jvz9 , 9actn-j1zqi7

Title : A specific molecular beacon probe for the detection of human prostate cancer cells - Jiang_2012_Bioorg.Med.Chem.Lett_22_3632
Author(s) : Jiang YL , McGoldrick CA , Yin D , Zhao J , Patel V , Brannon MF , Lightner JW , Krishnan K , Stone WL
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :3632 , 2012
Abstract : The small-molecule, water-soluble molecular beacon probe 1 is hydrolyzed by the lysate and living cells of human prostate cancer cell lines (LNCaP), resulting in strong green fluorescence. In contrast, probe 1 does not undergo significant hydrolysis in either the lysate or living cells of human nontumorigenic prostate cells (RWPE-1). These results, corroborated by UV-Vis spectroscopy and fluorescent microscopy, reveal that probe 1 is a sensitive and specific fluorogenic and chromogenic sensor for the detection of human prostate cancer cells among nontumorigenic prostate cells and that carboxylesterase activity is a specific biomarker for human prostate cancer cells.
ESTHER : Jiang_2012_Bioorg.Med.Chem.Lett_22_3632
PubMedSearch : Jiang_2012_Bioorg.Med.Chem.Lett_22_3632
PubMedID: 22572577

Title : Distribution of CuO nanoparticles in juvenile carp (Cyprinus carpio) and their potential toxicity - Zhao_2011_J.Hazard.Mater_197_304
Author(s) : Zhao J , Wang Z , Liu X , Xie X , Zhang K , Xing B
Ref : J Hazard Mater , 197 :304 , 2011
Abstract : Adverse effect of engineered nanoparticles (NPs) on the aquatic environment and organisms has recently drawn much attention. This paper reports on the toxicity of CuO NPs to juvenile carp (Cyprinus carpio) and their distribution in the fish. CuO NPs and its counterpart bulk particles (BPs) (10, 50, 100, 200, 300, 500 and 1000 mg L(-1)) exhibited no acute toxicity (96 h), while during the 30 day sub-acute toxicity test, carp growth was significantly inhibited by CuO NPs (100 mg L(-1)) in comparison to control, CuO BPs and Cu(2+) groups. CuO NPs (or released Cu(2+) ions inside the fish body) could distribute in various tissues/organs and followed an order: intestine>gill>muscle>skin and scale>liver>brain. For time-related distribution, Cu content (expressed on a dry mass basis) in intestine, gill and liver increased faster (within 1 day) and they had obviously higher Cu content than other tissues/organs at all exposure times. CuO NPs could be excreted by carp to lower their toxicity. Cholinesterase activity was inhibited during CuO NPs exposure, suggesting NPs exposure could have potential neurotoxicity, and free Cu(2+) ions dissolved inside the carp body was responsible for the cholinesterase inhibition. Finally, actual suspended NPs concentrations should be used instead of initially added concentrations whenever possible in nanotoxicity studies.
ESTHER : Zhao_2011_J.Hazard.Mater_197_304
PubMedSearch : Zhao_2011_J.Hazard.Mater_197_304
PubMedID: 22014442

Title : Comparative genomic and transcriptomic analysis revealed genetic characteristics related to solvent formation and xylose utilization in Clostridium acetobutylicum EA 2018 - Hu_2011_BMC.Genomics_12_93
Author(s) : Hu S , Zheng H , Gu Y , Zhao J , Zhang W , Yang Y , Wang S , Zhao G , Yang S , Jiang W
Ref : BMC Genomics , 12 :93 , 2011
Abstract : BACKGROUND: Clostridium acetobutylicum, a gram-positive and spore-forming anaerobe, is a major strain for the fermentative production of acetone, butanol and ethanol. But a previously isolated hyper-butanol producing strain C. acetobutylicum EA 2018 does not produce spores and has greater capability of solvent production, especially for butanol, than the type strain C. acetobutylicum ATCC 824.
RESULTS: Complete genome of C. acetobutylicum EA 2018 was sequenced using Roche 454 pyrosequencing. Genomic comparison with ATCC 824 identified many variations which may contribute to the hyper-butanol producing characteristics in the EA 2018 strain, including a total of 46 deletion sites and 26 insertion sites. In addition, transcriptomic profiling of gene expression in EA 2018 relative to that of ATCC824 revealed expression-level changes of several key genes related to solvent formation. For example, spo0A and adhEII have higher expression level, and most of the acid formation related genes have lower expression level in EA 2018. Interestingly, the results also showed that the variation in CEA_G2622 (CAC2613 in ATCC 824), a putative transcriptional regulator involved in xylose utilization, might accelerate utilization of substrate xylose.
CONCLUSIONS: Comparative analysis of C. acetobutylicum hyper-butanol producing strain EA 2018 and type strain ATCC 824 at both genomic and transcriptomic levels, for the first time, provides molecular-level understanding of non-sporulation, higher solvent production and enhanced xylose utilization in the mutant EA 2018. The information could be valuable for further genetic modification of C. acetobutylicum for more effective butanol production.
ESTHER : Hu_2011_BMC.Genomics_12_93
PubMedSearch : Hu_2011_BMC.Genomics_12_93
PubMedID: 21284892
Gene_locus related to this paper: cloab-CAC2917 , cloab-q97db4 , cloac-CAC0719 , cloac-CAC1022 , cloac-CAC1962 , cloac-CAC2246 , cloac-CAC3407 , cloac-CAP0071 , cloac-pnbae

Title : The effect of HSP-causing mutations in SPG3A and NIPA1 on the assembly, trafficking, and interaction between atlastin-1 and NIPA1 - Botzolakis_2011_Mol.Cell.Neurosci_46_122
Author(s) : Botzolakis EJ , Zhao J , Gurba KN , Macdonald RL , Hedera P
Ref : Molecular & Cellular Neurosciences , 46 :122 , 2011
Abstract : Despite its genetic heterogeneity, hereditary spastic paraplegia (HSP) is characterized by similar clinical phenotypes, suggesting that a common biochemical pathway underlies its pathogenesis. In support of this hypothesis, we used a combination of immunoprecipitation, confocal microscopy, and flow cytometry to demonstrate that two HSP-associated proteins, atlastin-1 and NIPA1, are direct binding partners, and interestingly, that the endogenous expression and trafficking of these proteins is highly dependent upon their coexpression. In addition, we demonstrated that the cellular distribution of atlastin-1:NIPA1 complexes was dramatically altered by HSP-causing mutations, as missense mutations in atlastin-1 (R239C and R495W) and NIPA1 (T45R and G106R) caused protein sequestration in the Golgi complex (GC) and endoplasmic reticulum (ER), respectively. Moreover, we demonstrated that HSP-causing mutations in both atlastin-1 and NIPA1 reduced axonal and dendritic sprouting in cultured rat cortical neurons. Together, these findings support the hypothesis that NIPA1 and atlastin-1 are members of a common biochemical pathway that supports axonal maintenance, which may explain in part the characteristic degeneration of long spinal pathways observed in patients with HSP.
ESTHER : Botzolakis_2011_Mol.Cell.Neurosci_46_122
PubMedSearch : Botzolakis_2011_Mol.Cell.Neurosci_46_122
PubMedID: 20816793

Title : Expression and characterization of a novel lipase from Aspergillus fumigatus with high specific activity - Shangguan_2011_Appl.Biochem.Biotechnol_165_949
Author(s) : Shangguan JJ , Liu YQ , Wang FJ , Zhao J , Fan LQ , Li SX , Xu JH
Ref : Appl Biochem Biotechnol , 165 :949 , 2011
Abstract : A novel lipase gene from Aspergillus fumigatus, afl1-1, was cloned and expressed with a molecular mass of 38 kDa in Escherichia coli for the first time. The recombinant lipase had a preference for short carbon chain p-nitrophenyl esters, especially toward C2 p-nitrophenyl ester and exhibited potent hydrolysis activity that had not been observed. The optimum pH and temperature of this new enzyme were 8.5 and 65 degrees C, respectively. The recombinant lipase (AFL1-1) is an alkaline enzyme which was stable in the pH range 6.0 approximately 8.5 for 16 h (at 4 degrees C) and at 30 approximately 50 degrees C for 1 h. It is an intracellular enzyme which was purified approximately 8.47-fold with an overall yield of 86.1% by single-step Ni-NTA affinity purification, with a very high specific activity of approximately 1.00 x 10(3) U mg(-1) on a standard substrate of p-nitrophenyl acetate. The Michaelis-Menten kinetic parameters V (max) and K (m) of the lipase were 1.37 mM mg(-1) min(-1) and 14.0 mM, respectively. Ca(2+) and other metal ions could not activate the lipase. According to the homology analysis and site-directed mutagenesis assay, the catalytic triad of the recombinant lipase was identified as Ser-165, Asp-260, and His-290 residues.
ESTHER : Shangguan_2011_Appl.Biochem.Biotechnol_165_949
PubMedSearch : Shangguan_2011_Appl.Biochem.Biotechnol_165_949
PubMedID: 21744116

Title : Significantly improved expression and biochemical properties of recombinant Serratia marcescens lipase as robust biocatalyst for kinetic resolution of chiral ester - Wang_2010_Appl.Biochem.Biotechnol_162_2387
Author(s) : Wang Y , Zhao J , Xu JH , Fan LQ , Li SX , Zhao LL , Mao XB
Ref : Appl Biochem Biotechnol , 162 :2387 , 2010
Abstract : A lipase gene from Serratia marcescens ECU1010 was cloned into expression vector pET28a, sequenced, and overexpressed as an N terminus His-tag fusion protein in Escherichia coli. Through the optimization of culture conditions in shake flask, the lipase activity was improved up to 1.09 x 10(5) U/l, which is a great improvement compared to our previous reports. It was purified to homogeneity by Ni-NTA affinity chromatography with an overall yield of 59.4% and a purification factor of 2.4-fold. This recombinant lipase displayed excellent stability below 30 degrees C and within the pH range of 5.0-6.8, giving temperature and pH optima at 40 degrees C and pH 9.0, respectively. The lipase activity was found to increase in the presence of metal ions such as Ca(2)+, Cu(2)+, and some nonionic surfactants such as PEG series. In addition, among p-nitrophenyl esters of fatty acids with varied chain length, the recombinant lipase showed the maximum activity on p-nitrophenyl laurate (C(1)(2)). Using racemic trans-3-(4'-methoxy-phenyl)-glycidyl methyl ester [(+/-)-MPGM] as substrate, which is a key chiral synthon for production of diltiazem, a 50% conversion yield was achieved after 4 h in toluene-water (100 mM KPB phosphate buffer, pH 7.5) biphasic system (5:5 ml) at 30 degrees C under shaking condition (160 rpm), affording (-)-MPGM in nearly 100% ee. The K(m) and V(max) values of the lipase for (+/-)-MPGM were 222 mM and 1.24 mmol min(-)(1) mg(-)(1), respectively. The above-mentioned features make the highly enantioselective lipase from Serratia marcescens ECU1010 a robust biocatalyst for practical use in large-scale production of diltiazem intermediate.
ESTHER : Wang_2010_Appl.Biochem.Biotechnol_162_2387
PubMedSearch : Wang_2010_Appl.Biochem.Biotechnol_162_2387
PubMedID: 20574813

Title : Inhibitory effects of thioethers on fatty acid synthase and 3T3-L1 cells - Sun_2010_J.Enzyme.Inhib.Med.Chem_25_290
Author(s) : Sun XB , Zhao J , Ma XF , Tian WX
Ref : J Enzyme Inhib Med Chem , 25 :290 , 2010
Abstract : Thioethers are the main flavor compounds found in Liliaceae Allium vegetables and have been shown to have beneficial effects against several diseases correlated with metabolic syndrome. The inhibitory effects of six thioethers on fatty acid synthase (FAS) were investigated. Dose-dependent and time-dependent inhibitions of FAS by one trisulfide and two disulfides were revealed. Diallyl trisulfide (DATS, IC(50) = 8.37 microM) was the most active of these thioethers. Inhibition kinetics, substrate protection analysis, and stoichiometric assay revealed that DATS interacted with both essential sulfhydryl groups on the acyl-carrier protein and beta-ketoacyl synthase domain of FAS to inactivate the enzyme. The inactivation by DATS represented affinity-labeling kinetics. The active thioethers also inhibited the differentiation and lipid accumulation of 3T3-L1 preadipocytes, and the effect was related to their inhibition of FAS. It is suggested that the inhibition on FAS by thioethers and Allium vegetables is an important factor for their effects against metabolic syndrome.
ESTHER : Sun_2010_J.Enzyme.Inhib.Med.Chem_25_290
PubMedSearch : Sun_2010_J.Enzyme.Inhib.Med.Chem_25_290
PubMedID: 19874137

Title : Adsorption and inhibition of butyrylcholinesterase by different engineered nanoparticles - Wang_2010_Chemosphere_79_86
Author(s) : Wang Z , Zhang K , Zhao J , Liu X , Xing B
Ref : Chemosphere , 79 :86 , 2010
Abstract : Butyrylcholinesterase (BChE), an important enzyme present in brain, serum and nervous system, is sensitive to neurotoxin. Engineered nanoparticles (NPs) may enter the mammalian body and be toxic. To investigate the potential neurotoxicity of different NPs and the interaction between NPs and BChE, three metal NPs (Cu-C, Cu and Al), three oxides NPs (SiO(2), TiO(2) and Al(2)O(3)), two carbon nanotubes (MWCNT and SWCNT) and two micro-scaled particles (Cu and activated carbon) were used to test their adsorption and inhibition on human serum BChE. At 800mgL(-1), adsorption and inhibition of BChE by MWCNT were the highest, 97% and 96%, respectively, while Al NPs showed the lowest adsorption (6.8%) and inhibition rates (3.3%). Ions could be dissolved in all metal and oxide NPs suspensions except TiO(2) NPs. In comparison to other ions, Cu(2+) released in Cu and Cu-C suspensions had the highest BChE activity reduction, 39.1% and 42.6%, respectively. The contribution of dissolved ions to the total inhibition by NPs suspension followed a decreasing sequence of Al (66%)>Cu (46%)>Cu-C (45%)>Al(2)O(3) (44%)>SS1[SiO(2)] (25%)>SP1[SiO(2)] (4%), suggesting that the inhibition of BChE may partly result from ion dissolution from NPs. The inhibition of BChE by micro-scaled activated carbon and Cu particles was significantly lower than that of their nano-scaled particles. The inhibition of BChE by MWCNT, SWCNT, TiO(2) (HR3) and Cu NPs showed concentration-response relationships. Their median inhibitory concentrations (IC(50)) were 97, 49, 206 and 1.54mgL(-1), respectively. These results indicate that these four NPs may have neurotoxicity and BChE may be potentially used as a biomarker of NPs in the environment.
ESTHER : Wang_2010_Chemosphere_79_86
PubMedSearch : Wang_2010_Chemosphere_79_86
PubMedID: 20089293

Title : Efficient production of (S)-naproxen with (R)-substrate recycling using an overexpressed carboxylesterase BsE-NP01 - Liu_2010_Appl.Biochem.Biotechnol_162_1574
Author(s) : Liu X , Xu JH , Pan J , Zhao J
Ref : Appl Biochem Biotechnol , 162 :1574 , 2010
Abstract : An (S)-enantioselective esterase from Bacillus subtilis ECU0554, named BsE-NP01, has been cloned and over-expressed in a heterologous host Escherichia coli BL21. BsE-NP01 was shown to be a carboxylesterase with a molecular mass of about 32 kDa, and temperature and pH optima at 50 degrees C and 8.5, respectively. It could catalyze the selective hydrolysis of the (S)-enantiomer of racemic naproxen methyl ester, giving optically pure (S)-naproxen with 98% enantiomeric excess. A mechanic-grinding approach to substrate dispersion was also reported, which was considered to be an alternative to take the place of deleterious surfactants such as Tween-80, with improved performance of the hydrolysis reaction. Batch production of (S)-naproxen was repeatedly carried out in a solid-water biphasic system at 2-L scale, achieving an average total yield of about 85% after ten runs with complete recycling of (R)-substrate.
ESTHER : Liu_2010_Appl.Biochem.Biotechnol_162_1574
PubMedSearch : Liu_2010_Appl.Biochem.Biotechnol_162_1574
PubMedID: 20237863
Gene_locus related to this paper: bacsu-cbxnp

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Adsorption and inhibition of acetylcholinesterase by different nanoparticles - Wang_2009_Chemosphere_77_67
Author(s) : Wang Z , Zhao J , Li F , Gao D , Xing B
Ref : Chemosphere , 77 :67 , 2009
Abstract : Manufactured nanoparticles can be toxic via interactions with proteins and enzymes. Acetylcholinesterase (AChE) is a key enzyme present in the brain, blood and nervous system. Therefore, adsorption and inhibition of AChE by eight nanoparticles, SiO(2), TiO(2), Al(2)O(3), Al, Cu, Cu-C (carbon-coated copper), multi-walled carbon nanotubes (MWCNT) and single-walled carbon nanotubes (SWCNT), were examined. A modified Ellman assay was used to measure AChE activity because nanoparticles could adsorb the yellowish product, 5'-mercapto-2'-nitrobenzoic acid (5-MNBA) during the color development. Adsorption and inhibition rates by nanoparticles were estimated by decrease of AChE activities compared to controls. Carbon nanotubes had high affinity for AChE adsorption, the highest being SWCNT (94%). Nano SiO(2) and Al(2)O(3) showed the lowest adsorption. Inhibition by the tested nanoparticles was primarily caused by adsorption. However, Cu(2+) release in Cu and Cu-C nanoparticle suspensions caused 40% and 45% of AChE activity reduction, respectively. AChE inhibition by bulk Cu and activated carbon particles was also measured for comparison, showing that the inhibition by bulk particles was lower than their counterpart nanoparticles. For bulk Cu particles, AChE inhibition was primarily caused by dissolved ions, but mainly by adsorption for activated carbon. AChE inhibition by Cu, Cu-C, MWCNT and SWCNT had dose-response relationships, and their median inhibitory concentrations (IC(50)) were 4, 17, 156 and 96mgL(-1), respectively, showing that these nanoparticles may have neurotoxicity and AChE may have potential to be used as a biomarker for nanoparticles.
ESTHER : Wang_2009_Chemosphere_77_67
PubMedSearch : Wang_2009_Chemosphere_77_67
PubMedID: 19540550

Title : The genome of the cucumber, Cucumis sativus L - Huang_2009_Nat.Genet_41_1275
Author(s) : Huang S , Li R , Zhang Z , Li L , Gu X , Fan W , Lucas WJ , Wang X , Xie B , Ni P , Ren Y , Zhu H , Li J , Lin K , Jin W , Fei Z , Li G , Staub J , Kilian A , van der Vossen EA , Wu Y , Guo J , He J , Jia Z , Tian G , Lu Y , Ruan J , Qian W , Wang M , Huang Q , Li B , Xuan Z , Cao J , Asan , Wu Z , Zhang J , Cai Q , Bai Y , Zhao B , Han Y , Li Y , Li X , Wang S , Shi Q , Liu S , Cho WK , Kim JY , Xu Y , Heller-Uszynska K , Miao H , Cheng Z , Zhang S , Wu J , Yang Y , Kang H , Li M , Liang H , Ren X , Shi Z , Wen M , Jian M , Yang H , Zhang G , Yang Z , Chen R , Ma L , Liu H , Zhou Y , Zhao J , Fang X , Fang L , Liu D , Zheng H , Zhang Y , Qin N , Li Z , Yang G , Yang S , Bolund L , Kristiansen K , Li S , Zhang X , Wang J , Sun R , Zhang B , Jiang S , Du Y
Ref : Nat Genet , 41 :1275 , 2009
Abstract : Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.
ESTHER : Huang_2009_Nat.Genet_41_1275
PubMedSearch : Huang_2009_Nat.Genet_41_1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5 , cucsa-a0a0a0lnt6 , cucsa-a0a0a0kpn7 , cucsa-a0a0a0lvt9 , cucsa-a0a0a0kdx8 , cucsa-a0a0a0m228 , cucsa-a0a0a0kz31 , cucsa-a0a0a0k5t5 , cucsa-a0a0a0kfs7 , cucsa-a0a0a0kjj7 , cucsa-a0a0a0kzs7 , cucsa-a0a0a0l0a6 , cucsa-a0a0a0l4w4 , cucsa-a0a0a0lpz0 , cucsa-a0a0a0ls66

Title : Biochemical toxicity of nano-anatase TiO2 particles in mice - Liu_2009_Biol.Trace.Elem.Res_129_170
Author(s) : Liu H , Ma L , Zhao J , Liu J , Yan J , Ruan J , Hong F
Ref : Biol Trace Elem Res , 129 :170 , 2009
Abstract : Previous research on the biological and toxic effects of nano-TiO(2) particles on animals only limit to a single dose. However, the toxicity caused by single dose nano-TiO(2) does not truly represent ecological and health effects of nano-TiO(2) retained in the environment. In order to further evaluate the toxicity of nano-TiO(2) particles, nano-anatase TiO(2) (5 nm) was injected into the abdominal cavity of ICR mice everyday for 14 days and the coefficients of organs and serum biochemical parameters were investigated. The results showed that, with increasing doses of nano-anatase TiO(2), the coefficients of liver, kidney, and spleen increased gradually, while the coefficients of lung and brain decreased gradually, and the coefficient of heart had little change. The order of the titanium accumulation in the organs was liver > kidneys > spleen > lung > brain > heart. The serum biochemical parameters with lower dose of nano-anatase TiO(2) showed little difference compared with the control mice, while with higher dose of nano-anatase TiO(2), the indicators of liver function, such as alkaline phosphatase, alanine aminotransferase, leucine acid peptide, pseudocholinesterase, total protein, and albumin level, were enhanced significantly; the indicators of kidney function, such as uric acid and blood urea nitrogen, were decreased; the activities of aspartate aminotransferase, creatine kinase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase, indicator of the myocardium function, were increased. The contents of triglycerides, glucose, and high-density lipoprotein cholesterol were significantly elevated. Taken together, nano-anatase TiO(2) in higher dose caused serious damage to the liver, kidney, and myocardium of mice and disturbed the balance of blood sugar and lipid in mice. The accumulation of titanium in the organs might be closely related to the coefficients of organs and the inflammatory responses of mice.
ESTHER : Liu_2009_Biol.Trace.Elem.Res_129_170
PubMedSearch : Liu_2009_Biol.Trace.Elem.Res_129_170
PubMedID: 19066734

Title : [Study on monitoring and clearing of organophosphate in blood in organophosphate poisoned rats] - Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
Author(s) : Zhang J , Zhao J , Zheng Y , Shao X
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 20 :413 , 2002
Abstract : OBJECTIVE: To study the new method of monitoring and clearing organophosphate in blood during single or mixed organophosphate(OP) poisoning. METHOD: (1) Mixed equal volumes of blood of OP poisoned rat and healthy rat, then determine whole blood cholinesterase (ChE) activity. The descending range of ChE activity represents the level of residual OP in blood. (2) Poisoned rats by single or mixed OP pesticides were injected with 5% NaHCO3 15 ml/kg intraperitoneally, then the level of OP in blood was detected.
RESULTS: (1) The monitoring results of blood residual OP by gas chromatography were similar to that by "Mixes blood method", which showed significant difference(P < 0.05) from that before OP administration. (2) NaHCO3 injection could not improve the toxic symptoms and whole blood or brain ChE inhibition in 10 CP poisoned rats, blood residual OP level was also not affected, but lung pathological changes by OP such as interstitial inflammation and oedema showed some relief. CONCLUSION: The monitoring of blood ChE by "mixed blood method" may reflect the general level of the blood residual OP within the range of exposure dose. The effect of NaHCO3 was not satisfactory, but it may improve OP-induced lung pathological changes.
ESTHER : Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
PubMedSearch : Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
PubMedID: 14694586

Title : A clinical analysis of 104 cases of acute pure and mixed organophosphate poisoning - Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
Author(s) : Zhang J , Zhao J , Sun S , Ma H , Zhao C , Guo Z , Wang F
Ref : Zhonghua Nei Ke Za Zhi , 41 :544 , 2002
Abstract : OBJECTIVE To study the difference of the clinical manifestations between single and mixed acute organophosphate (OP) poisoning. METHODS: The clinical signs and symptoms, the activity of cholinesterase (ChE) in erythrocytes, plasma and whole blood, and the level of AST, CK, LDH and ALT were compared between a single OP poisoning group (Group S) and a mixed OP poisoning group (Group C). RESULTS: Group S and Group C compare with: (1) Symptoms and signs on arrival at hospital: Group C was found to have more cases showing, nausea and vomiting than group S with obvious difference (P < 0.05). (2) The rates of other symptoms and signs were of no significant difference between the 2 groups. The activity of cholinesterase of the 2 groups on arrival at hospital: Whole blood ChE < 0.30: 16 cases and 14 cases; > 0.30 approximately : 24 cases and 19 cases; 0.50 approximately 0.70: 14 cases and 17 cases; erythrocyte ChE < 0.30: 18 cases and 14 cases; > 0.30 approximately : 22 cases and 21 cases; 0.50 approximately 0.70: 14 cases and 15 cases; plasma ChE < 0.30: 28 cases and 25 cases; > 0.30 approximately : 10 cases and 12 cases; 0.50 approximately 0.70: 16 cases and 13 cases; chi(2) = 0.852, 1.444, 0.509. There was no obvious difference (P > 0.05). (3) Positive rates of serum biochemical parameters between the 2 groups within 72 hours after arrival at hospital: Group S AST 24 cases, ALT 18 cases, CK 42 cases, LDH 22 cases, Tbil 21 cases; Group C AST 20 cases, ALT 11 cases, CK 32 cases, LDH 18 cases, Tbil 17 cases. There was also no obvious difference (P > 0.05). (4) Positive rate of ECG: between the 2 group on arrival at hospital Group S 24 cases, Group C 19 cases. No obvious difference was shown (P > 0.05). (5) Fatality rates between the 2 groups: Group S 7.41% (4/54), Group C 6.00% (3/50), chi(2) = 0.082, P > 0.05. CONCLUSION: Acute mixed OP poisoning and single OP poisoning show no significant difference in clinical manifestations. The treatment measures for single OP poisoning also has good effect fo mixed OP poisoning.
ESTHER : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedSearch : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedID: 12421504

Title : [Progress in the treatment of acute organophosphate poisoning] -
Author(s) : Zhang J , Zhao J
Ref : Zhonghua Yu Fang Yi Xue Za Zhi , 33 :248 , 1999
PubMedID: 15384239